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Molecular Profile Detail

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Profile Name ALK F1174I
Gene Variant Detail

ALK F1174I (gain of function)

Relevant Treatment Approaches ALK Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 F1174I ALK G1202R Advanced Solid Tumor resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Lorbrena (lorlatinib) in culture (PMID: 36201110). 36201110
EML4 - ALK ALK F1174I ALK G1202R Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xalkori (crizotinib) in culture (PMID: 36201110). 36201110
EML4 - ALK ALK F1174I ALK G1202R Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Alecensa (alectinib) in culture (PMID: 36201110). 36201110
EML4 - ALK ALK F1174I ALK G1202R Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to TPX-0131 in culture (PMID: 36201110). 36201110
EML4 - ALK ALK F1174I ALK G1202R Advanced Solid Tumor resistant Gilteritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK G1202R and F1174I were resistant to Xospata (gilteritinib) in culture (PMID: 36201110). 36201110