Molecular Profile Detail

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Profile Name ALK F1174L
Gene Variant Detail

ALK F1174L (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
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, a transformed cell line expressing ALK F1174L was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). 27049722
ALK F1174L neuroblastoma conflicting ALK Inhibitor Crizotinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Xalkori (crizotinib) did not inhibit growth of neuroblastoma cells over expressing ALK F1174L in culture, and only delayed tumor growth in patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, Lorbrena (lorlatinib) inhibited growth of neuroblastoma cells over expressing ALK F1174L in culture, and induced rapid and sustained complete tumor regression in both patient-derived and cell line xenograft models harboring ALK F1174L (PMID: 26554404). 26554404
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, Lorlatinib (PF-06463922) inhibited foci formation more efficiently than Xalkori (crizotinib) in transformed cells over expressing ALK F1174L in culture (PMID: 26554404). 26554404
ALK F1174L neuroblastoma sensitive ALK Inhibitor CEP-28122 Preclinical - Cell culture Actionable In a preclinical study, CEP-28122 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture (PMID: 22203728). 22203728
ALK F1174L neuroblastoma sensitive ALK Inhibitor AZD3463 Preclinical - Cell line xenograft Actionable In a preclinical study, AZD3463 inhibited growth of neuroblastoma cells harboring ALK F1174L in culture, resulted in near complete tumor regression in cell line xenograft models (PMID: 26786851). 26786851
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174L were resistant to Lorbrena (lorlatinib) in culture (PMID: 30322862). 30322862
ALK F1174L neuroblastoma conflicting ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase I/II trial (ADVL0912), Xalkori (crizotinib) treatment resulted in an objective response of 15% (3/20) in pediatric patients with relapsed/refractory neuroblastoma harboring ALK activating mutations or amplifications, although all 3 patients harboring ALK F1174L had disease progression after only 1 cycle of treatment (PMID: 33568345; NCT00939770). 33568345
ALK F1174L neuroblastoma no benefit ALK Inhibitor Crizotinib + Cyclophosphamide + Topotecan Case Reports/Case Series Actionable In a clinical case study, combination treatment with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan resulted in progressive disease within 1 cycle of therapy in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8 (PMID: 34210658). 34210658
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting 13 mo in a pediatric patient with metastatic, relapsed neuroblastoma harboring ALK F1174L and PIK3CA C692Ffs*8, who had previously progressed on combination therapy with Xalkori (crizotinib), Cytoxan (cyclophosphamide), and Topotecan (PMID: 34210658). 34210658
ALK F1174L Advanced Solid Tumor predicted - sensitive ALK Inhibitor TPX-0131 Preclinical - Biochemical Actionable In a preclinical study, TPX-0131 inhibited kinase activity of ALK F1174L in an in vitro assay (PMID: 34158340). 34158340
ALK F1174L neuroblastoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK F1174L (corresponds to F1178L in mouse) and subsequent upregulation of Ret (PMID: 24811913). 24811913
ALK F1174L neuroblastoma predicted - sensitive ALK Inhibitor Entrectinib Case Reports/Case Series Actionable In a Phase I/II trial, Rozlytrek (entrectinib) treatment resulted in a complete response in a patient with neuroblastoma harboring ALK F1174L (PMID: 35395680; NCT02650401). 35395680
ALK F1174L neuroblastoma conflicting ALK Inhibitor Crizotinib Case Reports/Case Series Actionable In a Phase Ib trial (PROFILE 1013), Xalkori (crizotinib) therapy resulted in stable disease lasting 19 months in a patient with advanced neuroblastoma harboring ALK F1174L (PMID: 29352732; NCT00939770). 29352732
ALK F1174L neuroblastoma sensitive ALK Inhibitor TQ-B3139 Preclinical - Cell line xenograft Actionable In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture and inhibited tumor growth in a cell line xenograft model (PMID: 30210922). 30210922
ALK F1174L neuroblastoma sensitive ALK Inhibitor Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) inhibited proliferation of a neuroblastoma cell line harboring ALK F1174L in culture (PMID: 31852910). 31852910
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor Repotrectinib Preclinical - Cell culture Actionable In a preclinical study, Repotrectinib (TPX-0005) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK F1174L in culture (PMID: 31852910). 31852910
ALK F1174L Advanced Solid Tumor predicted - sensitive ALK Inhibitor Conteltinib Preclinical - Biochemical Actionable In a preclinical study, Conteltinib (CT-707) inhibited ALK F1174L activity in an in vitro assay (PMID: 36424628). 36424628