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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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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
Clinical Trial Phase Therapies Title Recruitment Status
NCT02220894 Phase III Pemetrexed Carboplatin + Paclitaxel Pembrolizumab Study of MK-3475 (Pembrolizumab) Versus Platinum-based Chemotherapy for Participants With 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
NCT03520686 Phase II Pembrolizumab ALT-803 + Pembrolizumab QUILT-2.023: A Study of ALT-803, a Fusion Protein Activator of Natural Killer and T-Cells, in Combination With Pembrolizumab vs Pembrolizumab Alone as First-Line Treatment for Patients With Metastatic NSCLC. Recruiting
NCT01803282 Phase I Andecaliximab Fluorouracil + Leucovorin + Oxaliplatin + Pembrolizumab Carboplatin + Pemetrexed Fluorouracil + Irinotecan + Leucovorin Gemcitabine + Nab-paclitaxel Carboplatin + Paclitaxel Paclitaxel Bevacizumab Safety and Tolerability Study in Solid Tumors Completed
NCT02810457 Phase III 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 Subjects With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL) 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