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 F1174L ALK R1275Q neuroblastoma predicted - sensitive 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, and a patient harboring both ALK F1174L and ALK R1275Q stayed on treatment for 3 cycles until disease progression (PMID: 33568345; NCT00939770). 33568345
EML4 - ALK ALK R1275Q Advanced Solid Tumor sensitive TQ-B3139 Preclinical - Cell culture Actionable In a preclinical study, TQ-B3139 (CT-711) inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 30210922). 30210922
EML4 - ALK ALK R1275Q Advanced Solid Tumor sensitive APG-2449 Preclinical - Cell culture Actionable In a preclinical study, APG-2449 inhibited proliferation of cells expressing EML4-ALK with ALK R1275Q in culture (PMID: 35820889). 35820889
ALK R1275Q TP53 wild-type neuroblastoma sensitive Idasanutlin + TAE684 Preclinical - Cell culture Actionable In a preclinical study, the combination of TAE684 and Idasanutlin (RG7388) inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). 36602782
ALK R1275Q TP53 wild-type neuroblastoma sensitive Alectinib + Idasanutlin Preclinical - Cell culture Actionable In a preclinical study, Alecensa (alectinib) and Idasanutlin (RG7388) synergistically inhibited growth of a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture (PMID: 36602782). 36602782
ALK G1202R ALK R1275Q BRAF V600E neuroblastoma predicted - resistant Lorlatinib Case Reports/Case Series Actionable In a Phase I trial, a neuroblastoma patient harboring ALK R1275Q developed progressive disease on treatment with Lorbrena (lorlatinib) and was found to have acquired ALK G1202R and BRAF V600E via circulating tumor DNA (PMID: 37147298; NCT03107988). 37147298
ALK G1202R ALK R1275Q neuroblastoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing G1202R was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). 37147298
ALK L1196M ALK R1275Q neuroblastoma resistant Lorlatinib Preclinical - Cell culture Actionable In a preclinical study, a neuroblastoma cell line harboring ALK R1275Q and expressing L1196M was resistant to Lorbrena (lorlatinib) in culture (PMID: 37147298). 37147298
ALK R1275Q TP53 wild-type neuroblastoma sensitive Ceritinib + CGM097 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Zykadia (ceritinib) and CGM097 inhibited Alk signaling and resulted in synergistic inhibition of proliferation in a TP53 wild-type neuroblastoma cell line harboring ALK R1275Q in culture and induced tumor regression in a cell line xenograft model (PMID: 28425916). 28425916