Gene Variant Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Gene EML4 ALK
Variant EML4 - ALK
Impact List fusion
Protein Effect gain of function
Gene Variant Descriptions EML4-ALK results from the fusion of EML4 and ALK, resulting in constitutive kinase activity, transformation in cultured cells, and tumor formation in mouse models (PMID: 19064915, PMID: 17625570, PMID: 35138907). EML4-ALK fusions have been associated with non-small cell lung cancer (PMID: 26755435).
Associated Drug Resistance

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EML4 - ALK breast cancer predicted - sensitive Ceritinib + Fulvestrant Preclinical - Cell culture Actionable In a preclinical study, the addition of Zykadia (ceritinib) to Faslodex (fulvestrant) treatment in breast cancer cells expressing EML4-ALK restored growth inhibition in culture (PMID: 32348852). 32348852
EML4 - ALK Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640). 33627640
EML4 - ALK lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK variant 8 achieved a pathologic complete response following treatment with Xalkori (crizotinib), with a reduction in primary tumor size and pleural metastases within 1 month of treatment, and continuation of treatment for 5 years until death, after which cancer was not observed at autopsy (PMID: 31690489). 31690489
EML4 - ALK lung adenocarcinoma sensitive Dinaciclib Preclinical - Cell culture Actionable In a preclinical study, Dinaciclib (SCH 727965) treatment induced apoptosis, reduced viability, and inhibited proliferation in parental lung adenocarcinoma cells, and isogenic cells resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib), all harboring EML4-ALK in culture (PMID: 32558295). 32558295
EML4 - ALK papillary renal cell carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical study, three previously treated patients with metastatic papillary renal cell carcinoma harboring an EML4-ALK fusion were sensitive to treatment with Alecensa (alectinib), demonstrating a clinical and radiographic response in one patient, a radiographic response and ongoing stable disease for 9 months in another patient, and regression of multiple metastatic sites in the third patient (PMID: 29685646). 29685646
EML4 - ALK lung cancer predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response in a patient with metastatic lung cancer harboring EML4-ALK (PMID: 34378333). 34378333
EML4 - ALK lung adenocarcinoma sensitive Alvocidib Preclinical - Cell line xenograft Actionable In a preclinical study, Alvocidib (flavopiridol) treatment induced cell cycle arrest and apoptosis, reduced viability, and inhibited proliferation in both a parental lung adenocarcinoma cell line and isogenic lung adenocarcinoma cell lines resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib), all harboring EML4-ALK, in culture, and reduced tumor growth in Xalkori (crizotinib) and Alecensa (alectinib)-resistant cell line xenograft models (PMID: 32558295). 32558295
EML4 - ALK lung non-small cell carcinoma sensitive Alectinib + SHP099 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Alecensa (alectinib) and SHP099 inhibited downstream signaling and synergistically inhibited proliferation in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and resulted in increased suppression of tumor growth in cell line xenograft models compared to either agent alone (PMID: 34158345). 34158345
EML4 - ALK lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells harboring EML4-ALK fusion, and reduced intracranial tumor size in cell line xenograft models (PMID: 26144315). 26144315
EML4 - ALK lung non-small cell carcinoma sensitive Ensartinib + Sirolimus Preclinical Actionable In a preclinical study, transformed non-small cell lung cancer cells harboring EML4-ALK demonstrated enhanced growth inhibition to a combination treatment with Afinitor (sirolimus) and Ensartinib (X-396) (PMID: 21613408). 21613408
EML4 - ALK lung non-small cell carcinoma sensitive Ensartinib Phase II Actionable In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 59% (41/70; all partial responses) and stable disease in 31% (22/70) of patients with crizotinib-refractory non-small cell lung cancer harboring EML4-ALK (PMID: 31628085; NCT03215693). 31628085
EML4 - ALK lung squamous cell carcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment with whole-brain radiotherapy resulted in a partial response with a progression-free survival of 17 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK (PMID: 34376997). 34376997
EML4 - ALK lung non-small cell carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring EML4-ALK fusion in culture (PMID: 26090892). 26090892
EML4 - ALK Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 35421578). 35421578
EML4 - ALK Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK Advanced Solid Tumor sensitive Taletrectinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing EML4-ALK were sensitive to treatment with Taletrectinib (DS6051b) in culture, demonstrating cell growth inhibition (PMID: 31399568). 31399568
EML4 - ALK lung adenocarcinoma predicted - sensitive Alvocidib + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Alvocidib (flavopiridol) treatment in combination with Xalkori (crizotinib) reduced viability of Xalkori (crizotinib)-resistant lung adenocarcinoma cells harboring EML4-ALK in culture, but did not result in synergistic effects (PMID: 32558295). 32558295
EML4 - ALK lung non-small cell carcinoma sensitive Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited Alk phosphorylation and growth in non-small cell lung cancer cell lines harboring EML4-ALK in culture, and induced near complete tumor regression in cell line xenograft models (PMID: 27780853). 27780853
EML4 - ALK breast cancer resistant Fulvestrant Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing EML4-ALK demonstrated resistance to treatment with Faslodex (fulvestrant) in culture (PMID: 32348852). 32348852
EML4 - ALK lung non-small cell carcinoma sensitive Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited Alk phosphorylation and growth of a human non-small cell lung cancer cell line harboring EML4-ALK in culture and in cell line xenograft models (PMID: 21575866). 21575866
EML4 - ALK neuroblastoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of neuroblastoma cells harboring EML4-ALK in culture (PMID: 26554404). 26554404
EML4 - ALK Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK lung adenocarcinoma sensitive Lorlatinib Preclinical - Pdx Actionable In a preclinical study, Lorbrena (lorlatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). 34911818
EML4 - ALK breast cancer sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cells expressing EML4-ALK were sensitive to treatment with Zykadia (ceritinib) in culture, demonstrating inhibition of cell growth (PMID: 32348852). 32348852
EML4 - ALK Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK lung non-small cell carcinoma sensitive Alectinib + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Alecensa (alectinib) and Koselugo (selumetinib) inhibited tumor growth in cell line xenograft models of non-small cell lung cancer harboring EML4-ALK, but was less potent compared to treatment with the combination of Alecensa (alectinib) and SHP099 (PMID: 34158345). 34158345
EML4 - ALK Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK lung cancer predicted - sensitive Bevacizumab + Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a lung cancer patient with brain metastases harboring EML4-ALK who had developed resistance to treatment with Lorbrena (lorlatinib) after three months was subsequently treated with a combination of Avastin (bevacizumab) and Lorbrena (lorlatinib), and demonstrated a best response of stable disease, including disease control for 5.4 months, and 8% tumor shrinkage in the brain (PMID: 33283131). 33283131
EML4 - ALK large cell neuroendocrine carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in significant clinical improvement and a partial response in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK after 4 weeks of therapy, however, progression in bone metastasis developed at 4 months (PMID: 34994612). 34994612
EML4 - ALK lung non-small cell carcinoma sensitive MTI-31 Preclinical - Cell line xenograft Actionable In a preclinical study, MTI-31 inhibited proliferation and migration and increased PD-L1 degradation in a non-small cell lung cancer cell line harboring EML4-ALK in culture, and inhibited tumor growth in xenograft models (PMID: 30796032). 30796032
EML4 - ALK lung adenocarcinoma sensitive Brigatinib Preclinical - Pdx Actionable In a preclinical study, Alunbrig (brigatinib) treatment decreased tumor growth in a patient-derived xenograft (PDX) model of lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). 34911818
EML4 - ALK lung non-small cell carcinoma sensitive XMU-MP-5 Preclinical - Cell line xenograft Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling, induced apoptosis, and inhibited proliferation of non-small cell lung caner cells harboring EML4-ALK in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836). 34845836
EML4 - ALK Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 35421578). 35421578
EML4 - ALK lung non-small cell carcinoma predicted - sensitive Crizotinib + Filgotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EML4-ALK in culture that had, over time, acquired resistance to Xalkori (crizotinib) showed decreased drug resistance when treatment was combined with Filgotinib (GLPG0634), demonstrating reduced expression of Osmr and phosphorylated-Stat3, and decreased cell viability (PMID: 28729401). 28729401
EML4 - ALK pancreatic cancer predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in tumor shrinkage with treatment lasting eight months in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053). 34568053
EML4 - ALK lung non-small cell carcinoma sensitive WX-0593 Preclinical - Pdx Actionable In a preclinical study, WX-0593 inhibited tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK (PMID: 35421578). 35421578
EML4 - ALK lung adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 6.5 months in a patient with lung adenocarcinoma harboring EML4-ALK, who also harbored IDH1 R132H (PMID: 35324529). 35324529
EML4 - ALK lung adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 17.5 months in a patient with lung adenocarcinoma harboring EML4-ALK (PMID: 34911818). 34911818
EML4 - ALK malignant pleural mesothelioma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in symptom improvement and a partial response lasting 3.5 months in a patient with malignant pleural mesothelioma harboring EML4-ALK (PMID: 32600123). 32600123
EML4 - ALK lung non-small cell carcinoma sensitive Alectinib + RMC-4550 Preclinical - Cell culture Actionable In a preclinical study, the combination of Alecensa (alectinib) and RMC-4550 inhibited cell growth and downstream signaling in non-small cell lung cancer cell lines harboring EML4-ALK in culture (PMID: 34158345). 34158345
EML4 - ALK Advanced Solid Tumor sensitive Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensartinib (X-396) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191). 30002191
EML4 - ALK Advanced Solid Tumor predicted - sensitive NUV-655 Preclinical - Cell culture Actionable In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling, induced apoptosis, and inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 34845836). 34845836
EML4 - ALK lung squamous cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a complete response in the lung and partial response in the brain lesions in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, with a progression-free survival of 11 months (PMID: 34376997). 34376997
EML4 - ALK inflammatory myofibroblastic tumor predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with inflammatory myofibroblastic tumor harboring EML4-ALK achieved complete remission three years after starting Xalkori (crizotinib) treatment (PMID: 26808369). 26808369
EML4 - ALK lung cancer sensitive X-376 Preclinical - Cell line xenograft Actionable In a preclinical study, X-376 inhibited Alk signaling, resulted in growth inhibition in lung cancer cells harboring EML4-ALK fusion in culture and in cell line xenograft models (PMID: 21613408). 21613408
EML4 - ALK lung adenocarcinoma sensitive THZ1 Preclinical - Cell culture Actionable In a preclinical study, THZ1 treatment reduced viability and inhibited proliferation of parental lung adenocarcinoma, and isogenic cells resistant to Xalkori (crizotinib), Zykadia (ceritinib), and Alecensa (alectinib) cells, all harboring EML4-ALK, in culture (PMID: 32558295). 32558295
EML4 - ALK ovarian serous carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in decreased CA-125 and complete remission lasting more than 1 year in a patient with metastatic high-grade serous ovarian cancer harboring EML4-ALK (E13:E20), who previously progressed on chemotherapy (PMID: 32845005). 32845005
EML4 - ALK Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited growth of transformed cells expressing EML4-ALK in culture, led to tumor growth inhibition in cell line xenograft models (PMID: 30093503). 30093503
EML4 - ALK lung adenocarcinoma predicted - sensitive Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in a partial response lasting 8.7 months in a patient with lung adenocarcinoma harboring EML4-ALK, who progressed on prior Alecensa (alectinib) treatment (PMID: 34911818). 34911818
EML4 - ALK colorectal carcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in rapid clinical benefit and a partial response after 1 month of therapy in a patient with metastatic colorectal carcinoma harboring EML4-ALK, until disease progression after 4 months (PMID: 34036227). 34036227
EML4 - ALK lung non-small cell carcinoma sensitive Afatinib + Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, combination of Gilotrif (afatinib) and Alecensa (alectinib) restored sensitivity to Alecensa (alectinib) in non-small cell lung cancer cells harboring EML4-ALK fusion that acquired resistance to Alecensa (alectinib) through up-regulating Egfr signaling in culture, inhibited tumor progression in cell line xenograft models (PMID: 26682573). 26682573
EML4 - ALK pancreatic cancer predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in stable primary disease and decrease in brain lesions with treatment lasting nearly 10 months before progression of the brain metastases in a patient with pancreatic cancer harboring EML4-ALK (PMID: 34568053). 34568053
EML4 - ALK lung non-small cell carcinoma sensitive Crizotinib Phase I Actionable In a Phase I trial, Xalkori (crizotinib) inhibited tumor growth by at least 30% from baseline in 90% (18/20) of patients with EML4-ALK positive non-small cell lung carcinoma (PMID: 20979469; NCT00585195; NCT00585195). 20979469
EML4 - ALK lung non-small cell carcinoma sensitive Crizotinib Clinical Study - Cohort Actionable In a clinical study, non-small cell lung carcinoma patients harboring an EML4-ALK variant 1 (E13; A20, n=19) demonstrated a significantly longer progression-free survival (11.0 vs 4.2 months, p<0.05) compared to patients with a non-variant 1 EML4-ALK fusion (n=16) when treated with Xalkori (crizotinib) (PMID: 27354483). 27354483
EML4 - ALK Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 30002191). 30002191
EML4 - ALK lung non-small cell carcinoma sensitive CEP-28122 Preclinical - Cell line xenograft Actionable In a preclinical study, CEP-28122 inhibited growth of non-small cell lung carcinoma cell lines harboring EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 22203728). 22203728
EML4 - ALK neuroblastoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing EML4-ALK in culture (PMID: 26554404). 26554404
EML4 - ALK Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK in culture (PMID: 33627640). 33627640
EML4 - ALK lung squamous cell carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a partial response lasting 9.5 months in a patient with metastatic squamous cell lung cancer harboring EML4-ALK (PMID: 34324792). 34324792
EML4 - ALK lung non-small cell carcinoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited phosphorylation of Alk and inhibited growth of human non-small cell lung cancer cell lines harboring EML4-ALK in culture (PMID: 25173427). 25173427
EML4 - ALK colorectal carcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical benefit and a progression-free survival of 11.5 months in a patient with metastatic colorectal carcinoma harboring EML4-ALK, whose disease progressed on initial Xalkori (crizotinib) treatment and did not respond to subsequent Alecensa (alectinib) treatment (PMID: 34036227). 34036227
EML4 - ALK colon adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in clinical improvement after 1 month and a partial response lasting 8 months in a patient with colon adenocarcinoma harboring EML4-ALK (PMID: 33776709). 33776709
EML4 - ALK lung non-small cell carcinoma sensitive Entrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EML4-ALK were sensitive to Rozlytrek (entrectinib), resulting in inhibition of cell proliferation and complete tumor regression in cell line xenograft models (PMID: 26939704). 26939704
EML4 - ALK ALK G1269A lung non-small cell carcinoma sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, human lung cancer cell lines harboring EML4-ALK with ALK G1269A demonstrated sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In preclinical studies, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859, PMID: 26698910). 26698910 27009859
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578). 35421578
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 35421578). 35421578
EML4 - ALK ALK G1269A lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and growth of non-small cell lung cancer (NSCLC) cells over expressing ALK G1269A in the context of EML4-ALK in culture and in cell line xenograft models, as well as inhibited growth of patient derived NSCLC cells harboring EML4-ALK ALK G1269A in culture (PMID: 26144315). 26144315
EML4 - ALK ALK G1269A lung non-small cell carcinoma sensitive Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of a Xalkori (crizotinib)-resistant human non-small cell lung cancer cell line harboring an EML-ALK fusion with ALK G1269A in culture and induced tumor regression in cell line xenograft models (PMID: 26849637, PMID: 23344087). 26849637 23344087
EML4 - ALK ALK G1269A lung non-small cell carcinoma sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK fusion positive non-small cell lung cancer with ALK G1269A had a partial response to Alecensa (alectinib) treatment (PMID: 26849637). 26849637
EML4 - ALK ALK G1269A Advanced Solid Tumor predicted - resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated a decreased response when treated with Rozlytrek (entrectinib) compared to cells expressing wild-type EML4-ALK (PMID: 26939704). 26939704
EML4 - ALK ALK G1269A Advanced Solid Tumor predicted - resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 34845836). 34845836
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 27009859). 27009859
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture, and inhibited tumor growth in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1269A in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1269A lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK demonstrated stable disease when treated with Xalkori (crizotinib), but then progressed, and was found to harbor a secondary resistance mutation, ALK G1269A (PMID: 22235099). 22235099
EML4 - ALK ALK G1269A lung non-small cell carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, human lung cancer cell lines expressing ALK G1269A in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041). 24675041
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK in the context of EML4-ALK were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22235099). 22235099
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 inhibited growth of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1196M lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and proliferation of non-small cell lung carcinoma cells over expressing ALK L1196M in the context of EML4-ALK in culture, and resulted in tumor regression in cell line xenograft models (PMID: 26144315). 26144315
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK ALK L1196M (PMID: 21613408). 21613408
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were sensitive to Rozlytrek (entrectinib), resulting in anti-proliferative activity in culture (PMID: 26939704). 26939704
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M lung non-small cell carcinoma sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of non-small cell lung cancer cells expressing ALK L1196M in the context of EML4-ALK in culture (PMID: 21502504). 21502504
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell line xenograft Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836). 34845836
EML4 - ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were insensitive to Xalkori (crizotinib) as demonstrated by a lack of growth inhibition and Alk phosphorylation in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK L1196M demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 26698910) 26698910
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L196M in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing an EML4-ALK fusion and ALK L1196M in culture and in cell line xenograft models (PMID: 21575866). 21575866
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 24887559). 24887559
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1196M in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated decreased sensitivity to Alecensa (alectinib) compared to cells expressing EML4-ALK with wild-type ALK, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, EML4-ALK and ALK L1196M were identified as acquired mutations in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Xalkori (crizotinib) treatment (PMID: 28434515). 28434515
EML4 - ALK ALK L1196M lung non-small cell carcinoma sensitive Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) inhibited cell survival and PI3K/AKT, MEK/ERK, and mTOR signaling in two human non-small cell lung carcinoma cell lines harboring the Xalkori (crizotinib) resistance mutation EML4-ALK ALK L1196M in culture and inhibited tumor growth in xenograft models of one of those cell lines (PMID: 24675041). 24675041
EML4 - ALK ALK L1196M Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells over expressing ALK L1196M in the context of EML4-ALK in culture (European Journal of Cancer , Volume 69, S32). detail...
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were sensitive to Rozlytrek (entrectinib), resulting in anti-proliferative activity (PMID: 26939704). 26939704
EML4 - ALK ALK C1156Y Advanced Solid Tumor predicted - sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing ALK C1156Y in the context of EML4-ALK demonstrated minimal sensitivity to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4 - ALK ALK C1156Y Advanced Solid Tumor predicted - sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor predicted - sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor predicted - sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400). 25727400
EML4 - ALK ALK C1156Y lung non-small cell carcinoma no benefit Luminespib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with an ALK C1156Y secondary Xalkori (crizotinib) resistance mutation did not respond to Luminespib (AUY922) therapy (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 34845836). 34845836
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400). 25727400
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Ensartinib Preclinical Actionable In a preclinical study, Ensartinib (X-396) inhibited growth and Alk phosphorylation in cells expressing the Xalkori (crizotinib) resistance mutation, EML4-ALK C1156Y (PMID: 21613408). 21613408
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 inhibited growth of transformed cells expressing ALK C1156Y in the context of EML4-ALK in culture (PMID: 35421578). 35421578
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells expressing EML4-ALK with ALK C1156Y were sensitive to Alecensa (alectinib) in culture (PMID: 21575866). 21575866
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 24887559). 24887559
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400). 25727400
EML4 - ALK ALK C1156Y lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer developed resistance to Xalkori (crizotinib) with the emergence of ALK C1156Y, a secondary resistance mutation (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y lung non-small cell carcinoma sensitive Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation ALK C1156Y, was treated with Lorlatinib (PF-06463922) and displayed a 41% reduction in tumor growth after 5 weeks of treatment (PMID: 26698910; NCT01970865). 26698910
EML4 - ALK ALK C1156Y lung non-small cell carcinoma conflicting Ceritinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer with a secondary Xalkori (crizotinib) resistance mutation C1156Y, did not respond to Zykadia (ceritinib) therapy (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y lung non-small cell carcinoma conflicting Ceritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Zykadia (ceritinib) demonstrated tumor growth inhibition in xenograft models of a human non-small cell lung cancer cell line harboring EML4-ALK with ALK C1156Y when compared to Xalkori (crizotinib) (PMID: 24675041). 24675041
EML4 - ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK ALK C1156Y were insensitive to Xalkori (crizotinib) as demonstrated by lack of growth inhibition and lack of kinase inhibition in culture (PMID: 21613408). 21613408
EML4 - ALK ALK C1156Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y demonstrated moderate resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited proliferation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 25727400). 25727400
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth and ALK phosphorylation of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y in culture (PMID: 33627640). 33627640
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing S1206Y in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A demonstrated moderate resistance to Alecensa (alectinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor conflicting Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK S1206Y in culture and in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK S1206Y Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK S1206Y in culture (PMID: 25727400). 25727400
EML4 - ALK ALK S1206Y Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated growth inhibition with Zykadia (ceritinib) treatment in culture (PMID: 24675041). 24675041
EML4 - ALK ALK S1206Y Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK G1202R Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0131 inhibited Alk autophosphorylation and proliferation of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and resulted in complete tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to Rozlytrek (entrectinib) in culture (PMID: 26939704). 26939704
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578). 35421578
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK G1202R in the context of EML4-ALK in culture and reduced tumor growth in cell line xenograft models (PMID: 27780853). 27780853
EML4 - ALK ALK G1202R lung adenocarcinoma conflicting Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response and 30 months of progression-free survival in a lung adenocarcinoma patient harboring EML4-ALK and de novo ALK G1202R (PMID: 35235872). 35235872
EML4 - ALK ALK G1202R lung adenocarcinoma conflicting Brigatinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA, experienced disease progression after 2.5 months of Alunbrig (brigatinib) treatment, and only increased allelic frequency of ALK G1202R was detected at disease progression (PMID: 31585938). 31585938
EML4 - ALK ALK G1202R lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R (PMID: 35328235). 35328235
EML4 - ALK ALK G1202R lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) after the disease progressed on Alecensa (alectinib) treatment (PMID: 35328235). 35328235
EML4 - ALK ALK G1202R Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK G1202R in culture (PMID: 35421578). 35421578
EML4 - ALK ALK G1202R Advanced Solid Tumor sensitive Repotrectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited Alk activity and proliferation of transformed cells expressing ALK G1201R in the context of EML4-ALK in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 30093503). 30093503 detail...
EML4 - ALK ALK G1202R lung cancer conflicting Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis in transformed cells over expressing ALK G1202R in the context of EML4-ALK in culture and in cell line xenograft models (PMID: 26144315). 26144315
EML4 - ALK ALK G1202R lung cancer conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1202R lung non-small cell carcinoma sensitive HJC0152 Preclinical - Cell culture Actionable In a preclinical study, HJC0152 treatment decreased Stat signaling, migration, and invasion in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R in culture (PMID: 35085771). 35085771
EML4 - ALK ALK G1202R Advanced Solid Tumor predicted - sensitive NUV-655 Preclinical - Cell culture Actionable In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK G1202R in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK ALK G1202R lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK, who had developed resistance to Xalkori (crizotinib), was found to harbor ALK G1202R following treatment with Alecensa (alectinib) (PMID: 24736079). 24736079
EML4 - ALK ALK G1202R lung non-small cell carcinoma resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were insensitive to Zykadia (ceritinib) in culture (PMID: 24675041). 24675041
EML4 - ALK ALK G1202R lung non-small cell carcinoma resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who acquired the secondary drug resistance mutation, ALK S1206Y, when treated with Xalkori (crizotinib) was subsequently treated with Zykadia (ceritinib), developed drug resistance, and was then found to have lost the ALK S1206Y mutation, but gained ALK G1202R (PMID: 24675041). 24675041
EML4 - ALK ALK G1202R lung non-small cell carcinoma sensitive Ceritinib + HJC0152 Preclinical - Cell culture Actionable In a preclinical study, HJC0152 and Zykadia (ceritinib) combination treatment increased apoptosis and decreased viability and colony formation in a non-small cell lung cancer cell line expressing EML4-ALK and ALK G1202R compared to either drug alone in culture (PMID: 35085771). 35085771
EML4 - ALK ALK G1202R lung squamous cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK, who previously responded to Alunbrig (brigatinib) treatment (PMID: 34376997). 34376997
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1202R lung squamous cell carcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, third-line Lorbrena (lorlatinib) treatment resulted in a progression-free survival of 7 months in a patient with metastatic lung squamous cell carcinoma harboring EML4-ALK and ALK G1202R (PMID: 34376997). 34376997
EML4 - ALK ALK G1202R Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell line xenograft Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK G1202R in culture, and inhibited tumor growth in cell line xenograft models (PMID: 34845836). 34845836
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R demonstrated resistance to Alecensa (alectinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) did not effectively inhibit growth of transformed cells expressing EML4-ALK with ALK G1202R in culture, and did not inhibit tumor growth in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) treatment inhibited tumor growth in a mouse cell line xenograft model expressing EML4-ALK and ALK G1202R (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202R demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK G1202R Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing ALK I1171T in the context of EML4-ALK but to a lesser degree than cells expressing EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing EML4-ALK ALK I1171T in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell growth in patient derived non-small cell lung cancer cells harboring ALK I1171T in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK I1171T in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171T in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171T lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response with Xalkori (crizotinib) treatment, but after eight months showed progression, and was found to harbor a secondary resistance mutation, ALK I1171T (PMID: 25393798). 25393798
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171T demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to ASP3026 treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, XMU-MP-5 treatment decreased downstream signaling and inhibited proliferation of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 34845836). 34845836
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171T were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171T Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK I1171T was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK I1171T Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171T in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a brief response to Xalkori (crizotinib) treatment, but after 3 months showed tumor progression, and was found to harbor the secondary resistance mutation, ALK L1152R (PMID: 21791641). 21791641
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 21791641). 21791641
EML4 - ALK ALK L1152R lung cancer resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cells expressing ALK L1152R in the context of EML4-ALK demonstrated resistance to Zykadia (ceritinib) treatment in culture (PMID: 31925410). 31925410
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152R in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to Zykadia (ceritinib) in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152R demonstrated resistance to ASP3026 in culture (PMID: 25727400). 25727400
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152R in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152R Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK L1152R in culture (PMID: 25727400). 25727400
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578). 35421578
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive ASP3026 Preclinical - Cell culture Actionable In a preclinical study, ASP3026 inhibited growth of a transformed cell line expressing EML4-ALK with ALK V1180L in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 35421578). 35421578
EML4 - ALK ALK V1180L lung non-small cell carcinoma resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing EML4-ALK with ALK V1180L was resistant to Alecensa (alectinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK V1180L were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L lung non-small cell carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, a human non-small cell lung cancer cell line harboring ALK V1180L in the context of EML4-ALK was resistant to Xalkori (crizotinib) treatment in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive TAE684 Preclinical - Cell culture Actionable In a preclinical study, TAE684 inhibited growth of a transformed cell line expressing ALK V1180L in the context of EML4-ALK in culture (PMID: 25228534). 25228534
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK V1180L lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation, reduced proliferation, and induced apoptosis of non-small cell lung carcinoma cells harboring ALK V1180L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK V1180L Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK V1180L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib), but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796). 25393796
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK T1151M Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to ASP3026 in culture (PMID: 27009859). 27009859
EML4 - ALK ALK T1151M Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). 27009859
EML4 - ALK ALK T1151M Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4 - ALK ALK T1151M Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4 - ALK ALK T1151M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4 - ALK ALK T1151M Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174L in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) in culture (PMID: 27780853). 27780853
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture and in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174L Advanced Solid Tumor predicted - resistant XMU-MP-5 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L did not demonstrate sensitivity to treatment with XMU-MP-5 in culture (PMID: 34845836). 34845836
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were less sensitive to Alunbrig (brigatinib)-mediated growth inhibition compared to cells expressing EML4-ALK in culture (PMID: 27009859). 27009859
EML4 - ALK ALK F1174L Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174L in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK F1174L in the context of EML4-ALK in culture (PMID: 26144315). 26144315
EML4 - ALK ALK F1174L Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174L were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive AZD3463 Preclinical - Cell culture Actionable In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to Zykadia (ceritinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells overexpressing EML4-ALK with ALK R1192P in culture (PMID: 27009859). 27009859
EML4 - ALK ALK R1192P Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK R1192P were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K lung non-small cell carcinoma resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung carcinoma harboring EML4-ALK progressed on treatment with Xalkori (crizotinib) and was subsequently found to harbor a secondary resistance mutation, ALK E1210K (PMID: 29636358). 29636358
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK E1210K Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK E1210K demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK C1156Y ALK L1198F lung non-small cell carcinoma resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a patient with EML4-ALK positive non-small lung cancer with a secondary Xalkori (critzotinib) resistance mutation C1156Y, responded to Lorlatinib (PF-06463922) but subsequently developed resistance upon the emergence of a second ALK mutation, L1198F (PMID: 26698910; NCT01970865). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F lung non-small cell carcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small lung cancer initially responded to Xalkori (crizotinib) but developed resistance with the emergence of a secondary ALK mutation C1156Y, and subsequently redeveloped sensitivity to Xalkori (crizotinib) upon the emergence of a second ALK mutation, L1198F arising from resistance to Lorlatinib (PF-06463922) (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F in the context of EML4-ALK were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F in culture (PMID: 35726063). 35726063
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK C1156Y and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK C1156Y ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited growth of transformed cells expressing L1198F in the context of EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F demonstrated sensitivity to Alecensa (alectinib) treatment in culture (PMID: 27432227). 27432227
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor predicted - sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor predicted - sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F had reduced sensitivity to growth inhibition mediated by Lorbrena (lorlatinib) in comparison to wild-type EML4-ALK in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174C Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174C Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were sensitive to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated sensitivity to Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C Advanced Solid Tumor conflicting Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C demonstrated decreased sensitivity to Alecensa (alectinib) in culture compared to cells expressing EML4-ALK with wild-type ALK (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) modestly inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174C lung non-small cell carcinoma resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who developed resistance to Xalkori (crizotinib) treatment was subsequently treated with Zykadia (ceritinib), eventually progressed, and was found to have acquired ALK F1174C (PMID: 24675041). 24675041
EML4 - ALK ALK F1174C Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited growth of transformed cells expressing EML4-ALK with ALK F1174C in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were resistant to growth inhibition mediated by Xalkori (crizotinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK F1174C ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174C and ALK L1198F displayed enhanced resistance to growth inhibition by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F were resistant to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, introduction of an additional ALK mutation L1198F in transformed cells expressing ALK L1196M in the context of EML4-ALK reduced resistance to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1196M ALK L1198F Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R in the context of EML4-ALK were re-sensitized to Xalkori (crizotinib) mediated growth inhibition with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1198F and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Alunbrig (brigatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1198F displayed enhanced resistance to growth inhibition mediated by Lorbrena (lorlatinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1198F compound mutation in the context of EML4-ALK culture and resulted in only 30% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1198F and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1202R Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1198F and G1202R in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A in the context of EML4-ALK were re-sensitized and became modestly sensitive to Xalkori (crizotinib) with the introduction of an additional ALK mutation L1198F, in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Lorlatinib (PF-06463922) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Zykadia (ceritinib) in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK G1269A and L1198F in culture (PMID: 26698910). 26698910
EML4 - ALK ALK L1198F ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1269A and ALK L1198F were resistant to growth inhibition mediated by Alecensa (alectinib) in culture (PMID: 26698910). 26698910
EML4 - ALK SRC pos lung cancer resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines harboring EML4-ALK and elevated Src activity were resistant to Xalkori (crizotinib) induced growth inhibition in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4 - ALK SRC pos Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, lung cancer cell lines harboring EML4-ALK and elevated Src activity were resistant to Zykadia (ceritinib) induced growth inhibition in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4 - ALK SRC pos lung cancer sensitive Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, TPX-0005 inhibited Alk and Src signaling, and cell proliferation in lung cancer cell lines harboring EML4-ALK and elevated Src activity in culture (AACR, Cancer Res: April 2016; Volume 57, Abstract #2132). detail...
EML4 - ALK ALK I1171N Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor conflicting Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant Alectinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and did not induce tumor regression or reduce Alk phosphorylation in xenograft models (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798). 25393798
EML4 - ALK ALK I1171N lung non-small cell carcinoma sensitive Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171N lung non-small cell carcinoma resistant Entrectinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma resistant Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and induced tumor regression and suppressed Alk phosphorylation and downstream signaling in xenograft models (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1202del Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Alunbrig (brigatinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK G1202del Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK G1202del Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK G1202del Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated moderate resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK G1202del Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK G1202del demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK D1203N in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
EML4 - ALK ALK D1203N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK D1203N demonstrated sensitivity to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor decreased response Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C demonstrated a decreased response to treatment with Lorlatinib (PF-06463922) in culture compared to cells expressing wild-type EML4-ALK (PMID: 27432227). 27432227
EML4 - ALK ALK F1174C ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK F1174C did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated sensitivity to treatment with Lorlatinib (PF-06463922) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K did not response to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK D1203N ALK E1210K Advanced Solid Tumor decreased response Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK, ALK D1203N, and ALK E1210K demonstrated a decreased response to treatment with Alunbrig (brigatinib) when compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK S1206F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206F in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK S1206F lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in clinical improvement within one week of therapy, a 30.3% decrease in target lesion and a partial response after 2 months, and an ongoing response after 4 months in a patient with lung adenocarcinoma harboring de novo EML4-ALK-(E5;A20) and ALK S1206F (PMID: 27565908). 27565908
EML4 - ALK ALK L1152P Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152P Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1152P demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 24675041). 24675041
EML4 - ALK ALK L1152P Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK L1152P in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK L1152P Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK L1152P in culture (PMID: 35421578). 35421578
EML4 - ALK ALK L1152P Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1152P in the context of EML4-ALK demonstrated reduced sensitivity to Zykadia (ceritinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK T1151dup Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). 22277784
EML4 - ALK ALK T1151dup Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK T1151dup Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK T1151dup Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578). 35421578
EML4 - ALK ALK T1151dup Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578). 35421578
EML4 - ALK ALK T1151dup Advanced Solid Tumor sensitive Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK T1151dup (referred to as 1151insT) in culture and in xenograft models (PMID: 24887559). 24887559
EML4 - ALK ALK F1174V Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174V in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK F1174V Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174V were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V lung non-small cell carcinoma resistant Crizotinib Clinical Study Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated a partial response to Xalkori (crizotinib) treatment after 3 months, but then progressed, and was found to harbor the secondary resistance mutation, ALK F1174V (PMID: 24736079). 24736079
EML4 - ALK ALK F1174V lung non-small cell carcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK initially responded to Xalkori (crizotinib), but then progressed due to acquisition of the secondary resistance mutation, ALK F1174V, and then responded to treatment with Alecensa (alectinib), demonstrating a complete response in one lung nodule and a 44% decrease in size in a second lung nodule (PMID: 26464158). 26464158
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 35421578). 35421578
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK F1174V in the context of EML4-ALK in culture (PMID: 27780853). 27780853
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245C lung non-small cell carcinoma sensitive Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 that demonstrated resistance to treatment with Xalkori (crizotinib) after acquisition of ALK F1245C, achieved a complete radiographic response with no evidence of progression at 6 months following treatment with Zykadia (ceritinib) (PMID: 26775591). 26775591
EML4 - ALK ALK F1245C lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring EML4-ALK variant 3 demonstrated an initial response to treatment with Xalkori (crizotinib), but progressed after 27 months and was found to have acquired ALK F1245C (PMID: 26775591). 26775591
EML4 - ALK ALK I1171S ALK F1174V lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK F1174V initially responded to Alecensa (alectinib), but then demonstrated progression in one of two lung nodules, which was found to harbor a secondary resistance mutation, ALK I1171S, and upon resection of the nodule the patient continued Alecensa (alectinib) treatment and achieved complete remission (PMID: 26464158). 26464158
EML4 - ALK ALK L1196M ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK G1269A lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK demonstrated a partial response when treated with Xalkori (crizotinib), however, after 6 months the patient progressed and was found to harbor two secondary resistance mutations, ALK G1269A and ALK L1196M (PMID: 23344087). 23344087
EML4 - ALK ALK C1156Y ALK L1196M lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK treated on a clinical trial achieved a partial response when treated with Xalkori (crizotinib), however, after 5 months, the patient progressed and was found to harbor secondary resistance mutations, ALK C1156Y and ALK L1196M (PMID: 20979473; NCT00585195). 20979473
EML4 - ALK ALK C1156Y ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1198P Advanced Solid Tumor resistant TAE684 Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to TAE684 in culture (PMID: 21948233). 21948233
EML4 - ALK ALK L1198P Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells overexpressing ALK L1198P in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233). 21948233
EML4 - ALK ALK F1174V ALK G1202R lung non-small cell carcinoma sensitive Ceritinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung carcinoma patient harboring EML4-ALK who was previously treated with Xalkori (crizotinib) and subsequently developed the resistance mutation, ALK G1269A, was treated with Zykadia (ceritinib), later progressed, and was found to have lost ALK G1269A, but gained ALK F1174V and ALK G1202R (PMID: 24675041). 24675041
EML4 - ALK ALK C1156Y ALK I1171T Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK F1174C Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK F1174I Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174I was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK F1174V Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK D1203N was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A lung adenocarcinoma sensitive Lorlatinib + Saracatinib Preclinical - Patient cell culture Actionable In a preclinical study, Saracatinib (AZD0530) and Lorbrena (lorlatinib) synergistically inhibited viability of cells derived from the tumor from a patient with lung adenocarcinoma harboring EML4-ALK and acquired ALK C1156Y and G1269A compound mutation in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK C1156Y in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK C1156Y ALK G1269A lung adenocarcinoma unknown Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 6.9 months of therapy in a patient with lung adenocarcinoma harboring EML4-ALK, ALK C1156Y and ALK G1269A were identified in biopsies at disease progression, however, cells derived from the patient-derived xenograft (PDX) model of the patient and transformed cells expressing the compound mutation demonstrated sensitivity to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Rozlytrek (entrectinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK C1156Y ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK I1171S ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171S was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174C ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174C was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174L ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174L was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174V ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK F1174V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1179V ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1179V was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1256F was identified as a compound mutation in transformed cells expressing ALK L1196M in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK F1174C ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK G1269A was identified as a compound mutation in transformed cells expressing ALK F1174C in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell line xenograft Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1196M and ALK G1202R compound mutation in the context of EML4-ALK in culture, and resulted in complete tumor growth regression in a cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor sensitive NUV-655 Preclinical - Cell line xenograft Actionable In a preclinical study, NUV-655 treatment resulted in decreased growth in cells expressing both EML4-ALK and ALK G1202R and L1196M in culture and resulted in tumor regression in cell-line xenograft models (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK L1196M compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK L1196M were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and G1202R were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK L1196M was identified as a compound mutation in transformed cells expressing ALK G1202R in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK L1196M ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) treatment did not inhibit proliferation of transformed cells expressing ALK G1202R and L1196M compound mutation in the context of EML4-ALK in culture and resulted in only 18% tumor growth inhibition in a mouse cell line xenograft model (PMID: 34158340). 34158340
EML4 - ALK ALK I1171T ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171T was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorlatinib (PF-06463922) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, ALK I1171N was identified as a compound mutation in transformed cells expressing ALK G1269A in the context of EML4-ALK that acquired resistance to Lorbrena (lorlatinib) in culture (PMID: 29650534). 29650534
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK S1206C ALK E1210K lung non-small cell carcinoma resistant Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK and ALK E1210K eventually progressed on treatment with Alunbrig (brigatinib) and was subsequently found to have acquired another resistance mutation, ALK S1206C in cis (PMID: 29636358). 29636358
EML4 - ALK ALK F1174L ALK L1198V lung non-small cell carcinoma resistant Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK progressed while being treated with Alunbrig (brigatinib) and was subsequently found to harbor two resistance mutations, ALK F1174L and ALK L1198V, which were both in cis (PMID: 29636358). 29636358
EML4 - ALK FGFR1 amp lung non-small cell carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Alunbrig (brigatinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, FGFR1 amplification (PMID: 29636358). 29636358
EML4 - ALK HRAS amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring EML4-ALK treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor a presumed resistance alteration, HRAS amplification (PMID: 29636358). 29636358
EML4 - ALK ALK F1174L ALK G1269A lung adenocarcinoma predicted - resistant Belizatinib Case Reports/Case Series Actionable In a clinical case study, ALK F1174L and ALK G1269A were identified as newly acquired mutations in the pleural effusion from a patient with lung adenocarcinoma harboring an acquired EML4-ALK after his disease progressed on Belizatinib (TSR-011) treatment (PMID: 28434515). 28434515
EML4 - ALK ALK F1174L ALK D1203N ALK G1269A lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK D1203N were identified as a newly acquired mutation in the pleural effusion from a patient with lung adenocarcinoma after his disease progressed on Zykadia (ceritinib) treatment, in addition to the EML4-ALK, ALK F1174L, and ALK G1269A acquired after disease progression on Xalkori (crizotinib) and Belizatinib (TSR-011) sequentially (PMID: 28434515). 28434515
EML4 - ALK ALK E1303K lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a patient with non-small cell lung cancer harboring EML4-ALK and ALK E1303K developed progressive disease 7 days after Xalkori (crizotinib) treatment (PMID: 29978950). 29978950
EML4 - ALK ALK L1256F Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F lung adenocarcinoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) did not inhibit Alk kinase activity or proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002). 30662002
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1256F lung adenocarcinoma sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited Alk kinase activity and proliferation of lung adenocarcinoma cells expressing ALK L1256F in the context of EML4-ALK in cell culture (PMID: 30662002). 30662002
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 9.2 months in a patient with lung adenocarcinoma harboring EML4-ALK, at disease progression, ALK G1202R and ALK E1154K were identified in biopsies, while ALK G1202R and ALK I1268V were identified in ctDNA (PMID: 31585938). 31585938
EML4 - ALK ALK E1154K ALK G1202R ALK I1268V lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted rapid disease progression in a patient with lung adenocarcinoma harboring EML4-ALK, with acquired ALK G1202R and ALK E1154K in tumor biopsies, and ALK G1202R and ALK I1268V in ctDNA (PMID: 31585938). 31585938
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938). 31585938
EML4 - ALK ALK F1174L ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK F1174L and ALK G1202R compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK L1196M and ALK D1203N compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) in culture (PMID: 31585938). 31585938
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196M ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196M and D1203N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Xalkori (crizotinib) treatment in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S and G1269A in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Alecensa (alectinib) treatment in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and ALK G1269A demonstrated resistance to Lorbrena (lorlatinib) treatment in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S ALK G1269A Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S and G1269A were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK G1269S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911). 22034911
EML4 - ALK ALK G1269S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 21948233). 21948233
EML4 - ALK ALK G1269S Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK G1202R Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and C1156Y compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK C1156Y compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK G1202R Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK C1156Y and ALK G1202R compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK C1156Y ALK G1202R Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK C1156Y and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and ALK G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor predicted - sensitive NUV-655 Preclinical - Cell culture Actionable In a preclinical study, NUV-655 treatment resulted in decreased cell growth in a cell line expressing EML4-ALK fusion and ALK mutations, G1202R and G1296A, in culture (Cancer Res 2021;81(13_Suppl):Abstract nr 1468). detail...
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK G1269A were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A, L1204V, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1204V compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK G1202R, ALK L1204V, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK G1202R ALK L1204V ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1204V, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, G1269A, and L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK L1198F, ALK G1202R, and ALK G1269A compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1269A, L1198F, and G1202R compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK L1198F ALK G1202R ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK G1202R, L1198F, and G1269A compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK AXL over exp lung adenocarcinoma no benefit Bemcentinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib)-resistant lung adenocarcinoma cells harboring EML4-ALK and overexpressing AXL did not demonstrate sensitivity to Bemcentinib (BGB-324) treatment in culture (PMID: 32558295). 32558295
EML4 - ALK AXL over exp lung adenocarcinoma predicted - sensitive Bemcentinib + Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Bemcentinib (BGB-324) and Xalkori (crizotinib) combination treatment did not induce apoptosis, however, inhibited proliferation of Xalkori (crizotinib)-resistant lung adenocarcinoma cells harboring EML4-ALK and overexpressing AXL in culture (PMID: 32558295). 32558295
EML4 - ALK AXL over exp lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xospata (gilteritinib) inhibited cell growth, phosphorylation of Alk and Axl, and downstream signaling in a non-small cell lung cancer cell line harboring EML4-ALK and overexpressing AXL in culture and suppressed tumor growth in cell line xenograft models and inhibited tumor growth when administered to separate xenograft models that had previously demonstrated resistance to Alecensa (alectinib) treatment (PMID: 33627640). 33627640
EML4 - ALK AXL over exp lung non-small cell carcinoma resistant Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit cell growth, phosphorylation of Alk and Axl, or downstream signaling in a non-small cell lung cancer cell line harboring EML4-ALK and overexpressing AXL in culture, and did not inhibit tumor growth in cell line xenograft models (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK L1196Q demonstrated resistance to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK L1196Q lung non-small cell carcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and an acquired ALK L1196Q who progressed on prior Alecensa (alectinib) treatment, the response was ongoing after 17 months of treatment (PMID: 33209633). 33209633
EML4 - ALK ALK L1196Q lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic lung adenocarcinoma harboring EML4-ALK demonstrated disease progression following a 15-month partial response to Alecensa (alectinib) treatment, and was found to have acquired ALK L1196Q (PMID: 33209633). 33209633
EML4 - ALK ALK L1196Q Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK L1196Q in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK T1151K demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K lung adenocarcinoma predicted - resistant Ceritinib Case Reports/Case Series Actionable In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215). 28676215
EML4 - ALK ALK T1151K Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK T1151K was identified in the post-progression biopsy of a patient with lung adenocarcinoma harboring EML4-ALK after Xalkori (crizotinib) and Zykadia (ceritinib) therapies (PMID: 28676215). 28676215
EML4 - ALK ALK T1151K Advanced Solid Tumor sensitive Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK T1151K Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK T1151K in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1256F were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1256F Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1256F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Pdx Actionable In a preclinical study, Xospata (gilteritinib) induced complete tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I, and also induced tumor regression when administered to separate PDX tumors which had demonstrated resistance to Alecensa (alectinib) or Lorbrena (lorlatinib) treatment (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I lung non-small cell carcinoma predicted - resistant Alectinib Preclinical - Pdx Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174I were resistant to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174I lung non-small cell carcinoma predicted - resistant Lorlatinib Preclinical - Pdx Actionable In a preclinical study, Lorbrena (lorlatinib) failed to inhibit tumor growth in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring EML4-ALK and expressing ALK I1171N and F1174I (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198H in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor predicted - resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198H Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198H were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1174I were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1174I Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1174I in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK F1245V Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L demonstrated resistance to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and F1174L were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK F1174L Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and F1174L in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Alecensa (alectinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Zykadia (ceritinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Lorbrena (lorlatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor predicted - resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, Xalkori (crizotinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor conflicting Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK were resistant to Xalkori (crizotinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor sensitive TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing ALK I1171N and ALK L1198F compound mutation in the context of EML4-ALK in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and ALK L1198F in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N and L1198F compound mutation in the context of EML4-ALK were resistant to Alunbrig (brigatinib) treatment in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N ALK L1198F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1198F demonstrated resistance to treatment with Alunbrig (brigatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and L1196M were resistant to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M malignant pleural mesothelioma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in tumor regression and a partial response lasting 3.6 months in a patient with malignant pleural mesothelioma harboring EML4-ALK, ALK L1196M, and ALK I1171N (PMID: 32600123). 32600123
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor sensitive Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M Advanced Solid Tumor sensitive Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N and L1196M in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N ALK L1196M malignant pleural mesothelioma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK L1196M and ALK I1171N were identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK who previously responded to Alecensa (alectinib) treatment (PMID: 32600123). 32600123
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Alectinib Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK D1203N and F1245V in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Zykadia (ceritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor predicted - resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V demonstrated resistance to treatment with Xospata (gilteritinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK D1203N ALK F1245V Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK D1203N and F1245V were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK TP53 Q331* lung non-small cell carcinoma sensitive Alectinib + Ixazomib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Alecensa (alectinib) and Ninlaro (ixazomib) inhibited the proliferation of non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* in culture (PMID: 33310890). 33310890
EML4 - ALK TP53 Q331* lung non-small cell carcinoma resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33310890). 33310890
EML4 - ALK TP53 Q331* lung non-small cell carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890). 33310890
EML4 - ALK TP53 V274fs lung non-small cell carcinoma sensitive Alectinib + Ixazomib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination therapy of Alecensa (alectinib) and Ninlaro (ixazomib) inhibited the proliferation of non-small cell lung cancer cells harboring EML4-ALK and TP53 Q331* in culture and resulted in tumor regression in cell line xenograft models, with 3/8 achieving complete tumor regression (PMID: 33310890). 33310890
EML4 - ALK TP53 V274fs lung non-small cell carcinoma resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274fs were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33310890). 33310890
EML4 - ALK TP53 V274fs lung non-small cell carcinoma resistant Alectinib Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung cancer cells harboring EML4-ALK and TP53 V274* were resistant to treatment with Alecensa (alectinib), demonstrating cell growth in culture and tumor growth in cell line xenograft models (PMID: 33310890). 33310890
EML4 - ALK ALK S1206R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell line xenograft Actionable In a preclinical study, transformed cells expressing ALK S1206R in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture and in cell line xenograft models (PMID: 22034911). 22034911
EML4 - ALK ALK Q1188_L1190del lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in significant metabolic response and stable disease lasting 11 months in an EML4-ALK-positive lung adenocarcinoma patient harboring ALK Q1188_L1190del who had previously progressed on Xalkori (crizotinib) and Zykadia (ceritinib) treatment (PMID: 33887694). 33887694
EML4 - ALK ALK G1202K lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, fourth-line Lorbrena (lorlatinib) treatment resulted in symptom improvement and response in lung disease with a progression-free survival lasting 4 months in an EML4-ALK positive a patient with lung adenocarcinoma patient harboring EML4-ALK and an acquired ALK G1202K, who had previously progressed on Xalkori (crizotinib) and Alecensa (alectinib) treatment (PMID: 33790576). 33790576
EML4 - ALK ALK A1200_G1201delinsW lung adenocarcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient harboring EML4-ALK who developed resistance to Alecensa (alectinib) following acquisition of ALK A1200_G1201delinsW demonstrated symptom improvement and stable disease for 4 months with Alunbrig (brigatinib) treatment (PMID: 34548910). 34548910
EML4 - ALK ALK A1200_G1201delinsW lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, post treatment biopsy analysis of a lung adenocarcinoma patient initially harboring EML4-ALK who developed progressive disease after 20 months of Alecensa (alectinib) treatment revealed acquisition of ALK A1200_G1201delinsW (PMID: 34548910). 34548910
EML4 - ALK ALK V1180L ALK G1202R large cell neuroendocrine carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK developed progressive disease after initial response to Alecensa (alectinib) treatment, post-progression circulating tumor DNA analysis identified the acquisition of ALK V1180L and ALK G1202R, together with TP53 G105V and MYCN E378fs (PMID: 34994612). 34994612
EML4 - ALK ALK V1180L ALK G1202R large cell neuroendocrine carcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in clinical improvement and regression of lung lesions after 4 weeks of therapy in a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations; however, new bone lesions and progression of the brain mass was seen, and significant progressive disease developed after 3 months (PMID: 34994612). 34994612
EML4 - ALK ALK V1180L ALK G1202R large cell neuroendocrine carcinoma predicted - resistant Brigatinib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic large cell neuroendocrine carcinoma of the lung harboring EML4-ALK and acquired ALK V1180L and ALK G1202R mutations demonstrated further progressive disease 2 weeks after initiating Alunbrig (brigatinib) treatment (PMID: 34994612). 34994612
EML4 - ALK ALK C1156Y ALK L1196M ALK G1202R lung non-small cell carcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient with EML4-ALK, ALK G1202R, ALK L1196M, and ALK V1180L prior to Lorbrena (lorlatinib) treatment demonstrated loss of the V1180L variant and acquisition of ALK C1156Y following progression on Lorbrena (lorlatinib) (PMID: 31358542). 31358542
EML4 - ALK ALK L1319V colon adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with colon adenocarcinoma harboring EML4-ALK developed progressive disease after 8 months of Alecensa (alectinib) treatment, acquisition of ALK L1319V, KRAS amplification, KRAS Q61H, and NF1 Q20* were identified in post-progression biopsies (PMID: 33776709). 33776709
EML4 - ALK ALK I1171N ALK V1180L lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EML4-ALK, as well as IDH1 R132H, developed progressive disease after initial response to Alecensa (alectinib), and ALK I1171N and ALK V1180L were identified in the post-progression biopsy along with germline BRCA2 F2801fs (PMID: 35324529). 35324529
EML4 - ALK ALK F1174C ALK E1210K lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, ALK F1174C, and ALK E1210K (PMID: 34378333). 34378333
EML4 - ALK ALK I1171N ALK L1196M ALK G1202R malignant pleural mesothelioma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK G1202R was identified in the post-progression biopsy of a patient with malignant pleural mesothelioma harboring EML4-ALK with ALK L1196M and ALK I1171N who previously responded to Lorbrena (lorlatinib) treatment (PMID: 32600123). 32600123
EML4 - ALK ALK I1171N ALK D1203N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK D1203N Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK I1171N ALK D1203N Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N and ALK D1203N were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and ALK S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Lorbrena (lorlatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Xalkori (crizotinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alecensa (alectinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, G1269A, and S1206F were resistant to Alunbrig (brigatinib) in culture (PMID: 35726063). 35726063
EML4 - ALK ALK G1202R ALK S1206F ALK G1269A Advanced Solid Tumor resistant Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R, S1206F, and G1269A were resistant to Zykadia (ceritinib) in culture (PMID: 35726063). 35726063
ALK - SSH2 EML4 - ALK lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response, with shrinkage of the lesions, in a lung adenocarcinoma patient harboring two ALK fusions, EML4-ALK (e6:e20) and ALK-SSH2 (e19:e3) (PMID: 35144623). 35144623
EML4 - ALK ALK T1151K ALK G1202R ALK S1206F lung adenocarcinoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a clinical case study, ALK S1206F and ALK T1151K were identified in a patient with lung adenocarcinoma harboring EML4-ALK (e6a:e20) and ALK G1202R after the disease progressed on Lorbrena (lorlatinib) treatment (PMID: 35328235). 35328235
EML4 - ALK ALK G1202L lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, treatment with Lorbrena (lorlatinib) resulted in stable disease with a progression-free survival of 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK G1202L, which was acquired after prior ALK inhibitor therapy (PMID: 33380260). 33380260
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK fusion lung non-small cell carcinoma sensitive Brigatinib Phase Ib/II Actionable In a phase I/II clinical trial, Alunbrig (brigatinib) was determined to be safe and efficacious in patients with advanced, ALK-fusion positive NSCLC (PMID: 24091716). 24091716
ALK fusion lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). 28475456 detail...
ALK fusion lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). detail... detail... detail...
ALK fusion Erdheim-Chester disease sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). detail...
ALK fusion lung non-small cell carcinoma sensitive Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608). 33207094 detail... detail...
ALK fusion lung non-small cell carcinoma sensitive Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... 30413378 detail...
ALK fusion lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorlatinib (PF-06463922) demonstrated safety and resulted in a 50% (26/52) overall response rate in patients with ALK-positive or ROS1-positive non-small cell lung cancer, including intracranial responses in patients with CNS metastasis (J Clin Oncol 34, 2016 (suppl; abstr 9009)). detail...
ALK fusion lung adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in reduction of the lung tumors in a patient with metastatic ALK-positive lung adenocarcinoma, however, there was development of new brain metastases (PMID: 35373538). 35373538
ALK fusion Advanced Solid Tumor sensitive Entrectinib Case Reports/Case Series Actionable In a Phase I/II trial (STARTRK-NG), Rozlytrek (entrectinib) treatment was safe and resulted in an overall response rate (ORR) of 57.7% (15/26, 7 complete responses) with median duration of response and progression-free survival not reached in pediatric patients with CNS or extracranial solid tumors harboring fusions in NTRK1, NTRK2, NTRK3, ROS1, or ALK, ORR was 33.3% (1/3) in patients harboring ALK fusions (PMID: 35395680; NCT02650401). 35395680
ALK fusion Advanced Solid Tumor sensitive Entrectinib Phase I Actionable In a clinical study, combined analysis of 2 Phase I trials showed Rozlytrek (entrectinib) treatment resulted in an objective response rate of 57% (4/7) in patients with ALK rearranged advanced solid tumors that were treatment-naive, but no response (0/19) in patients who received prior Alk inhibitor treatments (PMID: 28183697). 28183697
ALK fusion Advanced Solid Tumor sensitive Entrectinib Phase I Actionable In a Phase I trial, Rozlytrek (entrectinib) treatment resulted in objective response in 67% (4/6) of patients with advanced solid tumors harboring rearrangement in ALK gene (AACR Apr 2016, Abstract # CT007). detail...
ALK fusion lung adenocarcinoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in shrinkage of the brain and spinal cord metastases in a patient with ALK-positive lung adenocarcinoma, who had been previously treated with Xalkori (crizotinib) (PMID: 35373538). 35373538
ALK fusion Erdheim-Chester disease sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). detail...
ALK fusion lung non-small cell carcinoma sensitive Ceritinib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Zykadia (ceritinib) resulted in a blinded independent review committee (BIRC)-assessed objective response rate of 44% (72/163) and a duration of response of 7.1 months in ALK-rearranged non-small cell lung cancer patients (PMID: 25754348; NCT01283516). detail... detail... 25754348
ALK fusion Erdheim-Chester disease sensitive Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). detail...
ALK fusion lung non-small cell carcinoma sensitive Alectinib Phase II Actionable In a Phase II trial, treatment with Alecensa (alectinib) resulted in a 49% (60/122) overall response rate in non-small cell lung cancer patients positive for an ALK fusion who had previously progressed on Xalkori (crizotinib) therapy (J Clin Oncol 33, 2015 (suppl; abstr 8008)) detail...
ALK fusion lung non-small cell carcinoma sensitive Alectinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangements (PMID: 28586279; NCT02075840). detail... 28586279 detail...
ALK fusion lung non-small cell carcinoma sensitive Alectinib Phase III Actionable In a Phase III trial, treatment with Alecensa (alectinib) resulted in improved progression-free survival compared to treatment with Xalkori (crizotinib) (HR=0.34) in ALK-positive non-small cell lung cancer patients (J Clin Oncol 34, 2016 (suppl; abstr 9008)). detail...
ALK fusion Erdheim-Chester disease sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). detail...
ALK fusion Erdheim-Chester disease sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as first-line or subsequent-line therapy for patients with Erdheim-Chester disease harboring ALK fusions (NCCN.org). detail...
ALK fusion anaplastic large cell lymphoma sensitive Crizotinib FDA approved Actionable In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). 28787259 detail...
ALK fusion inflammatory myofibroblastic tumor sensitive Crizotinib FDA approved Actionable In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770). 29352732 detail...
ALK fusion inflammatory myofibroblastic tumor sensitive Crizotinib FDA approved Actionable In a Phase I/II trial (Study ADVL0912) that supported FDA approval, Xalkori (crizotinib) therapy was safe and resulted in an objective response rate of 86% (12/14, 5 complete responses, 7 partial responses) and stable disease in 14% (2/14) of pediatric patients with ALK-positive unresectable inflammatory myofibroblastic tumors, with a median duration of response of 1.63 years (PMID: 28787259; NCT00939770). detail... 28787259
ALK fusion Advanced Solid Tumor predicted - sensitive Repotrectinib Phase I Actionable In a Phase I (TRIDENT-1) trial, Repotrectinib (TPX-0005) treatment resulted in stable disease in 25% (4/16) of patient with advanced solid tumor harboring ALK fusions who completed 2 cycles of treatment (J Clin Oncol 36, 2018 (suppl; abstr 2513); NCT03093116). detail...
ALK fusion lung non-small cell carcinoma sensitive Ensartinib Phase II Actionable In a Phase II trial, Ensartinib (X-396) treatment resulted in an objective response in 57% (43/75; all partial responses), and stable disease (SD) in 33% (25/75) of patients with crizotinib-refractory non-small cell lung cancer harboring an ALK fusion, with a response rate of 59% and SD rate of 31% in the 70 patients with EML4-ALK, and a response rate of 40% and SD rate of 60% in the 5 patients with non-EML4 ALK fusions (PMID: 31628085; NCT03215693). 31628085
ALK fusion lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in reduction of the brain metastases in a patient with ALK-positive lung adenocarcinoma who had been previously treated with Alecensa (alectinib) and Xalkori (crizotinib) (PMID: 35373538). 35373538
ALK fusion lung non-small cell carcinoma sensitive Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). 25470694 detail... detail...
ALK rearrange lung non-small cell carcinoma no benefit Osimertinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange colon mucinous adenocarcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with colon mucinous carcinoma harboring ALK rearrangement with a response duration of 103.3 weeks (PMID: 29352732; NCT00939770). 29352732
ALK rearrange lung non-small cell carcinoma no benefit Nivolumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org). 30596843 detail...
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines as preferred first-line and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase III trial (ALTA-1L) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in superior progression-free survival (HR=0.49, p=0.0007) compared to Xalkori (crizotinib) in patients with ALK-rearrangement positive metastatic non-small cell lung cancer (Ann Oncol., Apr 2019, 30 (Suppl 2):ii48; NCT02737501). detail... detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Phase Ib/II Actionable In a Phase I/II trial, Alunbrig (brigatinib) treatment resulted in an objective response rate of 100% (8/8) in ALK inhibitor-naive, ALK-rearranged non-small cell lung cancer (NSCLC) patients, 72% (51/71) in Xalkori (crizotinib) treated ALK-rearranged NSCLC patients, and 83% (5/6) in ALK-rearranged NSCLC patients with CNS metastases (PMID: 27836716; NCT01449461). 27836716
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Clinical Study Actionable In a retrospective analysis, Alunbrig (brigatinib) demonstrated limited efficacy, resulting in an objective response rate of 17% (3/18) and stable disease in 50% (9/18) of patients with Alecensa (alectinib) refractory, ALK-positive non-small cell lung cancer, with a median progression-free survival of 4.4 months (PMID: 29935304). 29935304
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (ALTA) that supported FDA approval, Alunbrig (brigatinib) treatment resulted in an overall response rate of 45% (51/112) in the 90mg arm and 54% (59/110) in the 180mg arm, and median progression-free survival of 9.2 and 11.0 months respectively, in ALK-rearranged (fusion) non-small cell lung carcinoma patients who progressed on Xalkori (crizotinib) (PMID: 28475456; NCT02094573). detail... 28475456
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alunbrig (brigatinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange lung non-small cell carcinoma sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange Advanced Solid Tumor sensitive Belizatinib Phase Ib/II Actionable In a Phase I trial, Belizatinib (TSR-011) treatment resulted in a response in 100% (3/3) of patients with ALK-rearranged advanced solid tumors when administered at higher doses, and stable disease for 7 months or longer in 56% (5/9) of patients at a lower dose (J Clin Oncol 33, 2015 (suppl; abstr 8063)). detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements (PMID: 30596843; ESMO.org). detail... 30596843
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Phase III Actionable In a Phase III trial (PROFILE 1014), Xalkori (crizotinib) treatment resulted in improved progression-free survival (PFS) (PFS=10.9 months, n=172) relative to chemotherapy (PFS=7.0 months, n=171) in NSCLC patients with ALK rearrangements, including patients with and without brain metastases at baseline, and improved intracranial disease rate in patients with brain metastases at baseline (PMID: 27022118; NCT01154140). 27022118
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Phase III Actionable In a Phase III trial, Xalkori (crizotinib) treatment resulted in improved objective response (87.5%, 90/103 vs 45.6%, 47/103) and median progression free survival (11.1 vs 6.8 mo) compared to pemetrexed, cisplatin and carboplatinin combination treatment in treatment-naive ALK positive advanced non-small cell lung carcinoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9058); NCT01639001). detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (PROFILE 1014) that supported FDA approval, Xalkori (crizotinib) treatment resulted in improved progression-free survival (10.9 vs 7.0 months, HR=0.45, p<0.001) and objective response rate (74% vs 45%) relative to chemotherapy in NSCLC patients with ALK rearrangements (PMID: 25470694; NCT01154140). detail... 25470694 detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement, or as a next-line therapy in patients with ALK-rearranged non-small cell lung cancer who have not received prior Xalkori (crizotinib) (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as first-line therapy for ALK rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Ceritinib + Crizotinib Clinical Study - Cohort Actionable In a retrospective analysis of patients with ALK-rearrangement positive non-small cell lung cancer, the combined median progression-free survival for sequential treatment with Xalkori (crizotinib) and Zykadia (ceritinib) without intervening treatments was 17.0 months, and overall survival was 49.4 months (PMID: 25724526). 25724526
ALK rearrange anaplastic large cell lymphoma not applicable N/A Guideline Prognostic The presence of ALK rearrangement is associated with a favorable prognosis in patients with anaplastic large cell lymphoma (NCCN.org). detail...
ALK rearrange anaplastic large cell lymphoma not applicable N/A Guideline Diagnostic ALK rearrangement aids in the diagnosis of anaplastic large cell lymphoma (NCCN.org). detail...
ALK rearrange Advanced Solid Tumor predicted - sensitive TQ-B3101 Phase I Actionable In a Phase I trial, TQ-B3101 treatment was well tolerated and resulted in an objective response rate (ORR) of 62.5% (15/24) in patients with advanced solid tumors harboring ALK or ROS rearrangement or MET amplification, also with an ORR of 62.5% (5/8) in patients with brain metastases (J Clin Oncol 38, 2020 (suppl 15; abstr e21705); NCT03019276). detail...
ALK rearrange lung non-small cell carcinoma predicted - sensitive PLB1003 Phase I Actionable In a Phase Ia trial, PLB1003 demonstrated safety and preliminary efficacy, resulted in a disease control rate of 86% (12/14, 10 partial response, 2 stable disease) in patients with ALK-rearranged non-small cell lung cancer who progressed on or did not tolerate previous treatment (Journal of Thoracic Oncology, Volume 14, Issue 10, S651). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive Ceritinib Phase I Actionable In a Phase I trial, Zykadia (ceritinib) treatment was well tolerated and resulted in an overall response rate of 70% (7/10; 7 partial responses) and a disease control rate of 80% (8/10) in pediatric patients with inflammatory myofibroblastic tumor harboring ALK rearrangement, with median progression-free survival unreached (PMID: 34780709; NCT01742286). 34780709
ALK rearrange inflammatory myofibroblastic tumor sensitive Ceritinib Guideline Actionable Zykadia (ceritinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange epithelioid inflammatory myofibroblastic sarcoma predicted - sensitive Alectinib Case Reports/Case Series Actionable In a clinical case study, Alecensa (alectinib) treatment resulted in a complete response lasting 44.2 months in a pediatric patient with an ALK-rearranged epithelioid inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange lung non-small cell carcinoma no benefit Pembrolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange inflammatory myofibroblastic tumor sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange lung adenocarcinoma predicted - sensitive CT-707 Phase I Actionable In a Phase I trial, Conteltinib (CT-707) demonstrated safety and preliminary efficacy, resulting in an overall response rate of 77% (10/13, 1 complete response, 9 partial responses) and a disease control rate of 85% (11/13) in patients with ALK-rearranged lung adenocarcinoma (n=12) or malignant pleural mesothelioma (n=1), median progression-free survival was 13 months in patients with lung adenocarcinoma (PMID: 32181989). 32181989
ALK rearrange lung non-small cell carcinoma no benefit Afatinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange lung adenocarcinoma predicted - sensitive Bevacizumab + Lorlatinib Case Reports/Case Series Actionable In a clinical case study, a lung adenocarcinoma patient with brain metastasis harboring an ALK rearrangement, who had progressed on single agent Lorbrena (lorlatinib) treatment, demonstrated a partial response when treated with a combination of Lorbrena (lorlatinib) and Avastin (bevacizumab), with a 68% decrease in tumor size in the brain and a total duration of disease control for 9.1 months (PMID: 33283131). 33283131
ALK rearrange lung non-small cell carcinoma no benefit Ipilimumab + Nivolumab Guideline Actionable Immune checkpoint inhibitors including Keytruda (pembrolizumab), Tecentriq (atezolizumab), and the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) are not indicated for use as initial systemic therapy in non-small cell lung cancer patients harboring oncogenes, including ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with ALK-rearranged advanced or metastatic non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as first-line therapy for non-small cell lung cancer patients with ALK rearrangements, including patients with CNS involvement, and as subsequent therapy for patients that progress on Xalkori (crizotinib) (PMID: 30596843; ESMO.org). 30596843 detail...
ALK rearrange lung non-small cell carcinoma sensitive Alectinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial supporting FDA approval (ALEX), Alecensa (alectinib) treatment resulted in improved rate of progression-free survival compared to Xalkori (crizotinib) (68.4% vs 48.7%, HR=0.47), and median progression-free survival (25.7 vs 10.4 months) in non-small cell lung cancer patients harboring ALK rearrangement (PMID: 28586279; NCT02075840). 28586279 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive Alectinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Alecensa (alectinib), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange lung non-small cell carcinoma sensitive Alectinib Phase II Actionable In a Phase II trial, Alecensa (alectinib) treatment was effective in treating non-small cell lung cancer patients with ALK rearrangement, resulting in a 50% (61/122) objective response rate (ORR) in all patients, a 45% (43/96) ORR in Crizotinib-refractory patients, and an 83% (70/84) CNS disease control rate (PMID: 26598747). 26598747
ALK rearrange lung non-small cell carcinoma sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226; ESMO.org). 32169226 detail...
ALK rearrange lung small cell carcinoma predicted - sensitive Alectinib + Irinotecan Case Reports/Case Series Actionable In a clinical case study, treatment with the combination of Alecensa (alectinib) and Camptosar (irinotecan) resulted in a partial response with progression-free survival lasting longer than 6 months in a small cell lung carcinoma patient harboring an ALK rearrangement (PMID: 34729013). 34729013
ALK rearrange lung non-small cell carcinoma no benefit Erlotinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479
ALK rearrange lung non-small cell carcinoma sensitive Ensartinib Phase Ib/II Actionable In a Phase I/II trial, Ensartinib (X-396) treatment resulted in partial response in 60% (36/60) and stable disease in 21.7 % (13/60) of patients with ALK-positive non-small cell lung cancer, with a median progression-free survival of 9.2 months, and a response rate of 80% (12/15) in crizotinib-naïve patients and 69% (20/29) in patients with prior crizotinib treatment (PMID: 29563138; NCT01625234). 29563138
ALK rearrange lung non-small cell carcinoma sensitive Ensartinib Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients with brain metastases harboring an ALK rearrangement demonstrated prolonged survival following treatment with the combination of an ALK-targeted tyrosine kinase inhibitor, including Ensartinib (X-396), and radiotherapy (PMID: 26438117). 26438117
ALK rearrange lung non-small cell carcinoma sensitive Ensartinib Guideline Actionable Ensartinib (X-396) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement (PMID: 32169226, Version Update 15 Sept 2020; ESMO.org). 32169226 detail...
ALK rearrange lung non-small cell carcinoma sensitive Ensartinib Phase III Actionable In a Phase III trial, Ensartinib (X-396) treatment significantly improved progression-free survival in patients with ALK-positive non-small cell lung cancer (25.8 vs 12.7 mo, HR 0.51, p<0.001) compared to Xalkori (crizotinib), and resulted in an intracranial response rate of 63.6% (7 of 11) in patients with target brain metastases at baselinewith compared to 21.1% (4 of 19) with Xalkori (crizotinib) (PMID: 34473194; NCT02767804). 34473194
ALK rearrange malignant pleural mesothelioma no benefit CT-707 Case Reports/Case Series Actionable In a Phase I trial, Conteltinib (CT-707) treatment resulted in disease progression after 1 cycle in a patient with ALK-rearranged malignant pleural mesothelioma (PMID: 32181989). 32181989
ALK rearrange anaplastic large cell lymphoma sensitive Alectinib Guideline Actionable Alecensa (alectinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). detail...
ALK rearrange thyroid gland medullary carcinoma predicted - sensitive Crizotinib Case Reports/Case Series Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in a partial response in a patient with medullary thyroid carcinoma harboring ALK rearrangement with a response duration of 16.1 weeks (PMID: 29352732; NCT00939770). 29352732
ALK rearrange lung non-small cell carcinoma predicted - sensitive SAF-189s Phase Ib/II Actionable In a Phase I/II trial, SAF-189 was well tolerated in ALK-positive non-small cell lung cancer patients, and resulted in a disease control rate (DCR) of 100% and median progression-free survival (PFS) of 33.1 mo in ALK inhibitor (ALKi)-naive and 22.1 mo in ALKi-pretreated patients in Phase I, and a DCR of 98.1% and 88.5%, and objective response rate of 92.3% and 65.4%, in ALKi-naive or crizotinib-pretreated patients, respectively, in Phase II (J Clin Oncol 40, 2022 (suppl 16; abs 9076); NCT04237805). detail...
ALK rearrange lung non-small cell carcinoma no benefit Gefitinib Guideline Actionable EGFR tyrosine kinase inhibitors including Tarceva (erlotinib), Iressa (gefitinib), Gilotrif (afatinib), and Tagrisso (osimertinib) are not indicated for use as subsequent therapy in ALK rearranged non-small cell lung cancer patients who relapsed on Alecensa (alectinib), Xalkori (crizotinib), or Zykadia (ceritinib) (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Atezolizumab Guideline Actionable Immune checkpoint inhibitors including Opdivo (nivolumab), Keytruda (pembrolizumab), Tecentriq (atezolizumab), and Imfinzi (durvalumab) are not indicated for use as subsequent therapy in non-small cell lung cancer patients with ALK rearrangement (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma no benefit Atezolizumab Clinical Study - Cohort Actionable In a retrospective analysis, PD-1/PD-L1 inhibitors (Opdivo (nivolumab), Keytruda (pembrolizumab), Durvalumab (MEDI4736), or Tecentriq (atezolizumab)) resulted in lower objective response rate (3.6%, 1/28) in non-small cell lung cancer patients harboring EGFR mutations (22/28) or ALK rearrangement (6/28) compared to EGFR wild-type, ALK negative/unknown patients (23.3%, 7/30) (PMID: 27225694). 27225694
ALK rearrange anaplastic large cell lymphoma sensitive Crizotinib FDA approved Actionable In a Phase I/II trial that supported FDA approval, Xalkori (crizotinib) treatment resulted in an objective response rate (ORR) of 83% (5/6, all complete responses (CR)) at the 165 mg dose, and an ORR of 90% (18/20, 16 CR) at the 280 mg dose, in pediatric patients 1 years of age or older and young adults with relapsed or refractory ALK-positive anaplastic large cell lymphoma (PMID: 28787259; NCT00939770). 28787259 detail...
ALK rearrange anaplastic large cell lymphoma sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines as second-line and subsequent therapy for patients with anaplastic large cell lymphoma harboring ALK rearrangements (NCCN.org). detail...
ALK rearrange lymphoma predicted - sensitive Crizotinib Phase I Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) treatment resulted in an objective response rate of 52.9% (9/17, 8 complete responses, 1 partial response) and stable disease in 17.6% (3/17) of patients with advanced ALK-positive lymphomas, with a median duration of response of 135.9 weeks in (PMID: 29352732; NCT00939770). 29352732
ALK rearrange Advanced Solid Tumor sensitive ASP3026 Phase I Actionable In a Phase I trial, ASP3026 treatment resulted in a partial response in 50% (8/16) and stable disease in 44% (7/16) of patients with an advanced solid tumor harboring an ALK rearrangement or ALK F1174L (PMID: 26966027; NCT01284192). 26966027
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in an objective response in 46% (19/41) of patients with non-small cell lung carcinoma harboring an ALK rearrangement (PMID: 29074098; NCT03052608). 29074098
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase II trial that supported FDA approval, Lorbrena (lorlatinib) treatment resulted in an objective response (OR) rate of 47% (93/198; 4 CR, 89 PR) and a median time to overall first tumor response of 1.4 months, and an objective intracranial response rate of 63% (51/81) and median time to first intracranial response of 1.4 months in ALK-positive (rearrangement or fusion) non-small cell lung cancer patients who had received at least one prior ALK inhibitor therapy (PMID: 30413378; NCT01970865). detail... detail... 30413378
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines as preferred first-line therapy and as subsequent therapy for patients with advanced or metastatic ALK-rearranged non-small cell lung cancer (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Phase II Actionable In a Phase II trial, Lorbrena (lorlatinib) treatment resulted in an intracranial disease control rate of 95% (21/22), intracranial objective response rate of 59% (13/22; 6 complete responses, 7 partial responses), a median intracranial progression-free survival (PFS) rate of 24.6 months, and a 12-month PFS rate of 79% in patients with ALK-rearranged non-small cell lung cancer, who previously demonstrated central nervous system progression on second-generation ALK inhibitors (PMID: 35584349; NCT02927340). 35584349
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in the Pan-Asian Guidelines Adaptation (PAGA) as subsequent therapy for patients who have progressed on second-generation ALK inhibitors (PMID: 30596843; ESMO.org). 30596843 detail...
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (Study B7461006) that supported FDA approval, Lorbrena (lorlatinib) treatment significantly improved 12-month progression-free survival rate (78% vs 39%, HR 0.28, p<0.001) compared to Xalkori (crizotinib) in patients with advanced ALK-positive non-small cell lung cancer who had no prior systemic therapy, objective response rate was 82% (57/69) with 71% achieved complete intracranial response in patients with brain metastasis (PMID: 33207094; NCT03052608). 33207094 detail... detail...
ALK rearrange lung non-small cell carcinoma sensitive Lorlatinib Guideline Actionable Lorbrena (lorlatinib) is included in guidelines for patients with metastatic non-small cell lung cancer harboring an ALK rearrangement who have progressed on an ALK tyrosine kinase inhibitor (PMID: 32169226; ESMO.org). detail... 32169226
ALK rearrange lung non-small cell carcinoma predicted - sensitive Ceritinib + Ribociclib Phase Ib/II Actionable In a Phase I/II trial, Zykadia (ceritinib) and Kisqali (ribociclib) combination therapy demonstrated a manageable safety profile and resulted in an overall response rate of 37.0% (10/27; 1 complete response and 9 partial responses) with a median progression-free survival of 21.5 months in patients with advanced ALK-rearranged non-small cell lung cancer (PMID: 35298959). 35298959
ALK rearrange inflammatory myofibroblastic tumor sensitive Brigatinib Guideline Actionable Alunbrig (brigatinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange lung non-small cell carcinoma sensitive WX-0593 Phase I Actionable In a Phase I trial, WX-0593 (iruplinalkib) demonstrated safety and resulted in an objective response rate (ORR) of 56.6% (56/99; all partial responses) and a disease control rate (DCR) of 83.8% (83/99), and median duration of response and median progression-free survival were not reached in non-small cell lung cancer patients with an ALK or ROS1-rearrangement, with an ORR of 58.2% (53/91; all partial responses) and DCR of 85.7% (78/91) in patients with an ALK rearrangement (PMID: 35087031; NCT03389815). 35087031
ALK rearrange lung non-small cell carcinoma no benefit Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive Crizotinib Guideline Actionable Xalkori (crizotinib) is included in guidelines for inflammatory myofibroblastic tumor patients with ALK translocations (NCCN.org). detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive Crizotinib Case Reports/Case Series Actionable In a clinical case study, Xalkori (crizotinib) treatment resulted in a partial response lasting 40 months in a pediatric patient with an ALK-rearranged inflammatory myofibroblastic tumor (PMID: 34036223). 34036223
ALK rearrange inflammatory myofibroblastic tumor sensitive Crizotinib FDA approved Actionable In a Phase I/II trial (Study ADVL0912) that supported FDA approval, Xalkori (crizotinib) therapy was safe and resulted in an objective response rate of 86% (12/14, 5 complete responses, 7 partial responses) and stable disease in 14% (2/14) of pediatric patients with ALK-positive unresectable inflammatory myofibroblastic tumors, with a median duration of response of 1.63 years (PMID: 28787259; NCT00939770). 28787259 detail...
ALK rearrange inflammatory myofibroblastic tumor sensitive Crizotinib FDA approved Actionable In a Phase Ib trial (PROFILE 1013) that supported FDA approval, treatment with Xalkori (crizotinib) resulted in an objective response rate of 66.7% (6/9, 1 complete response, 5 partial responses) and stable disease in 33.3% (3/9) of adult patients with advanced ALK-positive inflammatory myofibroblastic tumors, with a median duration of response of 74.1 weeks in (PMID: 29352732; NCT00939770). 29352732 detail...
ALK rearrange anaplastic large cell lymphoma