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Profile Name EML4 - ALK ALK I1171N
Gene Variant Detail

ALK I1171N (gain of function)

EML4 - ALK (gain of function)

Relevant Treatment Approaches Brigatinib Ceritinib 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 I1171N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated a decreased response to treatment with Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Ceritinib Ceritinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Zykadia (ceritinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated resistance to treatment with Alecensa (alectinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Brigatinib Brigatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Alunbrig (brigatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N Advanced Solid Tumor conflicting Lorlatinib Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EML4-ALK and ALK I1171N demonstrated sensitivity to treatment with Lorbrena (lorlatinib) in culture (PMID: 27432227). 27432227
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, a patient with non-small cell lung carcinoma harboring EML4-ALK demonstrated tumor regression when treated with Alecensa (alectinib), but progressed seven months later, and was found to harbor a secondary resistance mutation, ALK I1171N (PMID: 25393798). 25393798
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing ALK I1171N in the context of EML4-ALK were resistant to TPX-0131 in culture (PMID: 34158340). 34158340
EML4 - ALK ALK I1171N Advanced Solid Tumor predicted - resistant Crizotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Alectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to treatment with Alecensa (alectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Ceritinib Ceritinib Preclinical - Cell culture Actionable In a preclinical study, Zykadia (ceritinib) inhibited viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N 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 I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor conflicting Lorlatinib Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N demonstrated resistance to treatment with Lorbrena (lorlatinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Entrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N 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 in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant Alectinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Alecensa (alectinib) failed to inhibit growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and did not induce tumor regression or reduce Alk phosphorylation in xenograft models (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma sensitive Gilteritinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xospata (gilteritinib) inhibited growth of patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture, and induced tumor regression and suppressed Alk phosphorylation and downstream signaling in xenograft models (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma resistant Crizotinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Xalkori (crizotinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma sensitive Lorlatinib Lorlatinib Preclinical - Patient cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited cell viability, decreased downstream ALK signaling, and induced apoptosis in patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N lung non-small cell carcinoma resistant Entrectinib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived non-small cell lung cancer cells harboring EML4-ALK with ALK I1171N were resistant to treatment with Rozlytrek (entrectinib) in culture (PMID: 33627640). 33627640
EML4 - ALK ALK I1171N 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 I1171N in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171N 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 I1171N in culture (PMID: 35421578). 35421578
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to Augtyro (repotrectinib) in culture (PMID: 36201110). 36201110
EML4 - ALK ALK I1171N Advanced Solid Tumor sensitive Ensartinib Preclinical - Cell culture Actionable In a preclinical study, Ensacove (ensartinib) inhibited Alk phosphorylation and viability of transformed cells expressing EML4-ALK with ALK I1171N in culture (PMID: 36201110). 36201110
EML4 - ALK ALK I1171N Advanced Solid Tumor resistant TPX-0131 Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing EML4-ALK with ALK I1171N were resistant to TPX-0131 in culture (PMID: 36201110). 36201110
EML4 - ALK ALK I1171N lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171N was identified in post-progression biopsy in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20), who previously responded to Alecensa (alectinib) (PMID: 36864442). 36864442
EML4 - ALK ALK I1171N lung adenocarcinoma predicted - sensitive Ensartinib Case Reports/Case Series Actionable In a clinical case study, Ensacove (ensartinib) treatment resulted in a decrease in the liver lesions after 20 days of treatment in a patient with metastatic lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 36864442). 36864442
EML4 - ALK ALK I1171N inflammatory myofibroblastic tumor predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171N was identified on post-progression biopsy in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK, who previously responded to Alecensa (alectinib) (PMID: 37255276). 37255276
EML4 - ALK ALK I1171N inflammatory myofibroblastic tumor predicted - sensitive Lorlatinib Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in near resolution of the pleural effusion and decrease in pleural mass in a patient with inflammatory myofibroblastic tumor of the lung harboring EML4-ALK and ALK I1171N (PMID: 37255276). 37255276
EML4 - ALK ALK I1171N pulmonary neuroendocrine tumor predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171N was identified in post-progression biopsy in a patient with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20) who previously responded to Alecensa (alectinib) treatment (PMID: 35832448). 35832448
EML4 - ALK ALK I1171N pulmonary neuroendocrine tumor predicted - sensitive Ceritinib Ceritinib Case Reports/Case Series Actionable In a clinical case study, Zykadia (ceritinib) treatment resulted in response after 1 month of treatment with tumor shrinkage in a patient with metastatic pulmonary atypical carcinoid tumor harboring EML4-ALK (e6:e20) and ALK I1171N (PMID: 35832448). 35832448
EML4 - ALK ALK I1171N lung adenocarcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171N was identified at the time of progression in a patient with metastatic lung adenocarcinoma harboring EML4-ALK who previously demonstrated a partial response on Alecensa (alectinib) treatment (PMID: 38623748). 38623748
EML4 - ALK ALK I1171N lung adenocarcinoma predicted - sensitive Brigatinib Brigatinib Case Reports/Case Series Actionable In a clinical case study, Alunbrig (brigatinib) treatment resulted in stable disease with a progression-free survival of 17 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171N (PMID: 38623748). 38623748
EML4 - ALK ALK I1171N lung adenocarcinoma predicted - sensitive Lorlatinib Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in all lesions including lesions within the CNS with a progression-free survival of 14 months in a patient with metastatic lung adenocarcinoma harboring EML4-ALK and ALK I1171N (PMID: 38623748). 38623748
EML4 - ALK ALK I1171N lung non-small cell carcinoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a clinical case study, ALK I1171N was identified in the post-progression biopsy of a patient with non-small cell lung cancer harboring EML4-ALK who was treated with Alecensa (alectinib) (PMID: 33166721). 33166721
EML4 - ALK ALK I1171N sarcoma predicted - resistant Alectinib Case Reports/Case Series Actionable In a Phase II trial, ALK I1171N was identified on post-progression biopsy in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20), who previously achieved a partial response on Alecensa (alectinib) treatment (PMID: 39188081). 39188081
EML4 - ALK ALK I1171N sarcoma predicted - sensitive Lorlatinib Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a partial response in a patient with metastatic non-myofibroblastic sarcoma harboring EML4-ALK (e2:e20) and ALK I1171N (PMID: 39188081). 39188081
EML4 - ALK ALK I1171N Advanced Solid Tumor predicted - sensitive NVL-655 Preclinical Actionable In a preclinical study, NVL-655 moderately inhibited viability cells expressing EML4-ALK and ALK I1171N in culture and inhibited tumor growth in a transplant model (PMID: 39269178). 39269178