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Profile Name RET C634Y
Gene Variant Detail

RET C634Y (gain of function)

Relevant Treatment Approaches RET Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET C634Y Advanced Solid Tumor sensitive RET Inhibitor Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited proliferation of transformed cells harboring RET C634Y in culture (PMID: 23526464). 23526464
RET C634Y Advanced Solid Tumor sensitive RET Inhibitor HG-6-63-01 Preclinical Actionable In a preclinical study, HG-6-63-01 inhibited RET phosphorylation and downstream signaling and reduced proliferation of transformed cells expressing RET C634Y in culture (PMID: 26046350). 26046350
RET C634Y Advanced Solid Tumor sensitive RET Inhibitor XMD15-44 Preclinical Actionable In a preclinical study, XMD15-44 inhibited RET phosphorylation and downstream signaling and reduced proliferation of transformed cells expressing RET C634Y in culture (PMID: 26046350). 26046350
RET C634Y Advanced Solid Tumor sensitive RET Inhibitor ALW-II-41-27 Preclinical - Cell culture Actionable In a preclinical study, ALW-II-41-27 inhibited RET phosphorylation and downstream signaling, reduced proliferation of transformed cells expressing RET C634Y in culture (PMID: 26046350). 26046350
RET C634Y medullary thyroid carcinoma predicted - sensitive RET Inhibitor Sorafenib Case Reports/Case Series Actionable In a Phase II trial, Nexavar (sorafenib) treatment resulted in stable disease in one patient with medullary thyroid carcinoma harboring RET C634Y (PMID: 20368568; NCT00390325). 20368568
RET C634Y medullary thyroid carcinoma sensitive RET Inhibitor Selpercatinib FDA approved - On Companion Diagnostic Actionable In a Phase I/II trial (LIBRETTO-001) that supported FDA approval, Retevmo (selpercatinib) treatment resulted in an objective response rate (ORR) of 69% (38/55, 5 complete and 33 partial responses) in previously treated adult and pediatric patients of 12 years and older with medullary thyroid cancer harboring RET mutations as detected by an approved test, including RET C634Y; ORR was 73% (64/88) in treatment naive patients (PMID: 32846061; NCT03157128). detail... detail... 32846061