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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 conflicting 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
ALK F1174L neuroblastoma sensitive ALK Inhibitor Cyclophosphamide + Doxorubicin + Lorlatinib + Vincristine Sulfate Preclinical Actionable In a preclinical study, the combination of Lorbrena (lorlatinib), Cytoxan (cyclophosphamide), Adriamycin (doxorubicin), and Oncovin (vincristine) resulted in an early tumor response, and improved survival in a genetically engineered mouse model of neuroblastoma harboring ALK F1174L (PMID: 36602782). 36602782
ALK F1174L neuroblastoma conflicting 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 a complete response after 2 cycles in a one pediatric patient, and a clinical response with stable disease lasting 7 months in another pediatric patient with relapsed neuroblastoma harboring ALK F1174L (PMID: 36765519). 36765519
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in stable disease after 4 cycles in a pediatric patient with neuroblastoma harboring ALK F1174L (PMID: 36765519). 36765519
ALK F1174L neuroblastoma conflicting ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment resulted in a minor response with stable disease in a neuroblastoma patient harboring ALK F1174L (PMID: 37147298; NCT03107988). 37147298
ALK F1174L neuroblastoma sensitive ALK Inhibitor Ceritinib + Ribociclib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zykadia (ceritinib) and Kisqali (ribociclib) synergistically inhibited proliferation and Alk phosphorylation and induced cell cycle arrest in neuroblastoma cell line harboring ALK F1174L in culture, and induced complete tumor regression and increased event-free survival compared to either agent alone (P<0.0001) in a cell line xenograft model (PMID: 27986745). 27986745
ALK F1174L neuroblastoma sensitive ALK Inhibitor 4SC-205 + Ceritinib Preclinical - Cell culture Actionable In a preclinical study, the combination of 4SC-205 and Zykadia (ceritinib) inhibited viability to a greater degree than either therapy alone in neuroblastoma cell lines harboring ALK F1174L (PMID: 34709738). 34709738
ALK F1174L neuroblastoma sensitive ALK Inhibitor 4SC-205 + Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of 4SC-205 and Lorbrena (lorlatinib) inhibited viability to a greater degree than either therapy alone in neuroblastoma cell lines harboring ALK F1174L (PMID: 34709738). 34709738
ALK F1174L Advanced Solid Tumor sensitive ALK Inhibitor CCC-003 Preclinical - Cell culture Actionable In a preclinical study, CCC-003 inhibited viability in transformed cells expressing ALK F1174L in culture (PMID: 34591871). 34591871
ALK F1174L neuroblastoma sensitive ALK Inhibitor CCC-003 Preclinical - Cell line xenograft Actionable In a preclinical study, CCC-003 treatment resulted in decreased cell proliferation and induction of apoptosis in neuroblastoma cell lines harboring ALK F1174L in culture, and inhibited tumor growth in a cell line xenograft model (PMID: 34591871). 34591871
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 in 3 of 5 patients and a partial response in 1 of 5 patients with neuroblastoma harboring ALK F1174L (PMID: 37561984). 37561984