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Profile Name EML4 - ALK
Gene Variant Detail

EML4 - ALK (gain of function)

Relevant Treatment Approaches ALK Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 Advanced Solid Tumor sensitive ALK Inhibitor 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 cancer predicted - sensitive ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 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 lung adenocarcinoma predicted - sensitive ALK Inhibitor 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 Advanced Solid Tumor sensitive ALK Inhibitor 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 non-small cell carcinoma sensitive ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 Advanced Solid Tumor sensitive ALK Inhibitor 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 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 non-small cell carcinoma predicted - sensitive ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 ALK Inhibitor 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 ALK Inhibitor WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 inhibited growth of transformed cells expressing EML4-ALK in culture (Cancer Res 2018;78(13 Suppl):Abstract nr 4794). detail...
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor 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 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 neuroblastoma sensitive ALK Inhibitor 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 breast cancer predicted - sensitive ALK Inhibitor 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 lung non-small cell carcinoma sensitive ALK Inhibitor 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 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 non-small cell carcinoma sensitive ALK Inhibitor WX-0593 Preclinical - Pdx Actionable In a preclinical study, WX-0593 inhibited Alk downstream signaling and tumor growth in patient-derived xenograft (PDX) models of non-small cell lung cancer harboring EML4-ALK (Cancer Res 2018;78(13 Suppl):Abstract nr 4794). detail...
EML4 - ALK lung cancer sensitive ALK Inhibitor 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 non-small cell carcinoma sensitive ALK Inhibitor 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 ALK Inhibitor 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 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 lung adenocarcinoma conflicting ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Xalkori (crizotinib) and Zykadia (ceritinib)-resistant lung adenocarcinoma cell lines harboring EML4-ALK demonstrated resistance to Lorbrena (lorlatinib) treatment in culture, however, in Alecensa (alectinib)-resistant cells treatment led to reduced viability, and inhibited tumor growth in the cell line xenograft model with Xalkori (crizotinib) resistance (PMID: 32558295). 32558295
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor 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 Advanced Solid Tumor sensitive ALK Inhibitor 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 non-small cell carcinoma sensitive ALK Inhibitor 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 Advanced Solid Tumor sensitive ALK Inhibitor 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 inflammatory myofibroblastic tumor predicted - sensitive ALK Inhibitor 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 Advanced Solid Tumor sensitive DS6051b Preclinical - Cell culture Actionable In a preclinical study, cells expressing EML4-ALK were sensitive to treatment with DS6051b in culture, demonstrating cell growth inhibition (PMID: 31399568). 31399568
EML4 - ALK Advanced Solid Tumor sensitive ALK Inhibitor 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 predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, TPX-0131 inhibited proliferation of transformed cells expressing EML4-ALK in culture (AACR Virtual Annual Meeting II (Jun 2020), Abstract 52226). detail...
EML4 - ALK lung non-small cell carcinoma sensitive ALK Inhibitor 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 neuroblastoma resistant ALK Inhibitor 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 ALK Inhibitor 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 lung adenocarcinoma predicted - sensitive ALK Inhibitor 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 breast cancer sensitive ALK Inhibitor 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 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 Advanced Solid Tumor sensitive ALK Inhibitor 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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02220894 Phase III Carboplatin + Pemetrexed Disodium Carboplatin + Paclitaxel Pembrolizumab Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042) Active, not recruiting
NCT02684461 Phase II Pembrolizumab Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel Active, not recruiting
NCT02364999 Phase III Bevacizumab + Carboplatin + Paclitaxel A Comparative Study Of PF-06439535 Plus Paclitaxel-Carboplatin And Bevacizumab Plus Paclitaxel-Carboplatin Patients With Advanced Non-Squamous NSCLC Completed
NCT01803282 Phase I Andecaliximab Fluorouracil + Leucovorin + Oxaliplatin + Pembrolizumab Carboplatin + Pemetrexed Disodium Fluorouracil + Irinotecan + Leucovorin Gemcitabine + Nab-paclitaxel Carboplatin + Paclitaxel Paclitaxel Bevacizumab Safety and Tolerability Study in Solid Tumors Completed
NCT02810457 Phase III Carboplatin + FKB238 + Paclitaxel Bevacizumab + Carboplatin + Paclitaxel Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer (AVANA) Active, not recruiting
NCT03625323 Phase II Eftilagimod alpha + Pembrolizumab Combination Study With Soluble LAG-3 Fusion Protein Eftilagimod Alpha (IMP321) and Pembrolizumab in Patients With Previously Untreated Unresectable or Metastatic NSCLC, or Recurrent PD-X Refractory NSCLC or With Recurrent or Metastatic HNSCC (TACTI-002) Recruiting
NCT03666988 Phase I GSK3368715 First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL) Completed
NCT04686305 Phase I Durvalumab + Pemetrexed Disodium + Trastuzumab deruxtecan Carboplatin + Durvalumab + Trastuzumab deruxtecan Durvalumab + Trastuzumab deruxtecan Cisplatin + Durvalumab + Trastuzumab deruxtecan Phase Ib Study of the Safety of T-DXd and Durvalumab With Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC (DL03) Active, not recruiting