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Profile Name EML4 - ALK ALK F1174V
Gene Variant Detail

ALK F1174V (gain of function - predicted)

EML4 - ALK (gain of function)

Relevant Treatment Approaches Alectinib Brigatinib

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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 ALK F1174V Advanced Solid Tumor sensitive Brigatinib 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 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 lung non-small cell carcinoma predicted - sensitive Alectinib 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 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 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 sensitive Alectinib 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 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 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 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 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 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 Iruplinalkib Preclinical - Cell culture Actionable In a preclinical study, Iruplinalkib (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 Brigatinib 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 Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensartinib (X-396) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141). 31446141
EML4 - ALK ALK F1174V Advanced Solid Tumor sensitive Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK F1174V in culture (PMID: 31446141). 31446141
EML4 - ALK ALK F1174V lung adenocarcinoma predicted - sensitive Lorlatinib Case Reports/Case Series Actionable In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a complete response with a progression-free survival of 12.3 months, overall survival of 28.1 months, and a duration of treatment of 13.8 months in a patient with lung adenocarcinoma harboring EML4-ALK (e2:e20) with ALK F1174V (PMID: 39500140). 39500140