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Profile Name EML4 - ALK ALK I1171S
Gene Variant Detail

ALK I1171S (unknown)

EML4 - ALK (gain of function)

Relevant Treatment Approaches Lorlatinib

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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 I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant ASP3026 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to ASP3026 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant AZD3463 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to AZD3463 mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with EML4-ALK positive non-small cell lung cancer initially responded to Alecensa (alectinib), but progressed with the emergence of a secondary ALK I1171S mutation (PMID: 25393796). 25393796
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive Lorlatinib Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171S demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Zykadia (ceritinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) reduced ALK phosphorylation and inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 31943796). 31943796
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alunbrig (brigatinib)-mediated growth inhibition in culture (PMID: 27009859). 27009859
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171S in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive Lorlatinib Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171S were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S 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 I1171S in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171S Advanced Solid Tumor sensitive WX-0593 Preclinical - Cell culture Actionable In a preclinical study, WX-0593 treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171S Advanced Solid Tumor conflicting Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK I1171S in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171S lung adenocarcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171S was identified on post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK, who previously responded to Xalkori (crizotinib) (PMID: 36324562). 36324562
EML4 - ALK ALK I1171S lung adenocarcinoma predicted - sensitive Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in tumor shrinkage with a progression-free survival of at least 8 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171S (PMID: 36324562). 36324562
EML4 - ALK ALK I1171S lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171S was identified on post-progression biopsy in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e19) who previously responded to Alecensa (alectinib) treatment (PMID: 29981924). 29981924
EML4 - ALK ALK I1171S lung adenocarcinoma predicted - sensitive Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response with regression of the liver lesions and disease control in the intrathoracic and brain metastases lasting at least 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e19) and ALK I1171S (PMID: 29981924). 29981924