Molecular Profile Detail

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Profile Name ALK R1275Q
Gene Variant Detail

ALK R1275Q (gain of function)

Relevant Treatment Approaches ALK Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ALK mutant lung non-small cell carcinoma no benefit Crizotinib + Onalespib Phase II Actionable In a Phase II trial, Onalespib (AT13387) and Xalkori (crizotinib) combination treatment did not significantly improve median progression free survival (269 vs 266 days) or objective response rate (55.4%, 38/68 vs 45.3%, 31/68) compared to Xalkori (crizotinib) single treatment in patients with non-small cell lung carcinoma harboring either an ALK mutation or ALK rearrangement (J Clin Oncol 34, 2016 (suppl; abstr 9059); NCT01712217). detail...
ALK mutant lung non-small cell carcinoma no benefit Belizatinib Phase I Actionable In a Phase I trial, treatment with Belizatinib (TSR-011) in ALK inhibitor-naive non-small cell lung cancer patients (n=14) harboring either an ALK mutation, ALK amplification, or an ALK rearrangement resulted in a partial response in 6 patients and stable disease in 8 patients, however, it was determined that the drug resulted in limited efficacy and development of the drug was discontinued (PMID: 31217479; NCT02048488). 31217479
ALK act mut neuroblastoma predicted - sensitive Navitoclax + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) sensitized neuroblastoma cell lines harboring ALK activating mutations to Navitoclax (ABT-263), resulting in reduced cell viability in culture (PMID: 36895472). 36895472
ALK act mut neuroblastoma predicted - sensitive Trametinib + Venetoclax Preclinical - Cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an ALK activating mutation to Venclexta (venetoclax), resulting in reduced cell viability in culture (PMID: 36895472). 36895472
ALK act mut neuroblastoma predicted - sensitive S63845 + Trametinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Mekinist (trametinib) sensitized a neuroblastoma cell line harboring an ALK activating mutation to S63845 (MIK655), resulting in reduced cell viability in culture (PMID: 36895472). 36895472
ALK act mut neuroblastoma sensitive Lorlatinib Phase I Actionable In a Phase I trial, Lorbrena (lorlatinib) treatment was well tolerated and resulted in a modified response rate of 30% (7/23) in children and 67% (10/15) in adults with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L, F1245Y, F1245L, D1276_R1279delinsE, or amplification (PMID: 37012551; NCT03107988). 37012551
ALK act mut neuroblastoma sensitive Cyclophosphamide + Lorlatinib + Topotecan Phase I Actionable In a Phase I trial, the combination of Lorbrena (lorlatinib), Topotecan, and Cytoxan (cyclophosphamide) treatment was well tolerated and resulted in a modified response rate of 63% (5/8) in pediatric patients with neuroblastoma harboring an ALK activating mutation, including ALK F1174C, F1174L, R1275Q, or R1275L (PMID: 37012551; NCT03107988). 37012551
ALK act mut neuroblastoma predicted - sensitive NVL-655 Preclinical - Cell culture Actionable In a preclinical study, NUV-655 inhibited proliferation of neuroblastoma cell lines harboring activating mutations in ALK in culture (Cancer Res (2022) 82 (12_Supplement): 3337). detail...