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| Profile Name | EML4 - ALK |
| Gene Variant Detail | |
| Relevant Treatment Approaches | ALK Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| 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 | 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 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 | 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 | 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 | 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 | 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 | 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 | 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 | predicted - sensitive | ALK Inhibitor | 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 | papillary renal cell carcinoma | predicted - sensitive | ALK Inhibitor | 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 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 non-small cell carcinoma | sensitive | ALK Inhibitor | 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 | 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 | 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 | 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 | 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 | colorectal carcinoma | predicted - sensitive | ALK Inhibitor | 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 | 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 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 | 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 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 | 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 | 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 | 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 | lung non-small cell carcinoma | sensitive | ALK Inhibitor | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 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 | 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 |
| 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 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 | 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 | 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 | 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 | 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 | 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 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 | colorectal carcinoma | predicted - sensitive | ALK Inhibitor | 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 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT02684461 | Phase II | Pembrolizumab | Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel | Active, not recruiting | USA | 0 |
| 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 | 0 | |
| 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 | USA | CAN | 2 |
| 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) | Recruiting | USA | CAN | 10 |
| 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 | USA | 0 |
| 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 | USA | 26 |
| 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 | USA | 23 |
| 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 | USA | 5 |