Molecular Profile Detail

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Profile Name ALK F1174V
Gene Variant Detail

ALK F1174V (gain of function - predicted)

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 F1174V neuroblastoma sensitive ALK Inhibitor Brigatinib Preclinical - Cell culture Actionable In a preclinical study, neuroblastoma cells harboring ALK F1174V were sensitive to Alunbrig (brigatinib) in culture and in vivo, resulting in inhibition of both Alk activity and cell proliferation (PMID: 27049722). 27049722
ALK F1174V neuroblastoma predicted - sensitive 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, a patient harboring ALK F1174V stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770). 33568345
ALK F1174V neuroblastoma predicted - resistant ALK Inhibitor Repotrectinib Preclinical - Pdx Actionable In a preclinical study, a neuroblastoma patient-derived xenograft (PDX) model harboring ALK F1174V was resistant to treatment with Augtyro (repotrectinib) (PMID: 34482287). 34482287
ALK F1174V neuroblastoma predicted - sensitive ALK Inhibitor Irinotecan + Repotrectinib + Temozolomide Preclinical - Pdx Actionable In a preclinical study, combination treatment with Augtyro (repotrectinib), Camptosar (irinotecan), and Temodar (temozolomide) resulted in inhibition of tumor growth in a patient-derived xenograft (PDX) model of neuroblastoma harboring ALK F1174V (PMID: 34482287). 34482287
ALK F1174V neuroblastoma sensitive ALK Inhibitor Lorlatinib Case Reports/Case Series Actionable In a clinical case study, Lorbrena (lorlatinib) treatment resulted in a complete response lasting greater than 20 months in a patient with neuroblastoma harboring ALK F1174V (PMID: 37561984). 37561984
ALK F1174V neuroblastoma sensitive ALK Inhibitor Lorlatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Lorbrena (lorlatinib) treatment inhibited proliferation of a neuroblastoma cell line harboring ALK F1174V in culture and inhibited tumor growth in a cell line xenograft model (PMID: 27483357). 27483357
ALK F1174V neuroblastoma sensitive ALK Inhibitor Entrectinib Preclinical - Cell culture Actionable In a preclinical study, Rozlytrek (entrectinib) treatment inhibited ALK phosphorylation, downstream signaling, and viability of a neuroblastoma cell line harboring ALK F1174V in culture (PMID: 35085006). 35085006