Molecular Profile Detail

Profile Name PDGFRA D842V
Gene Variant Detail

PDGFRA D842V (gain of function)

Relevant Treatment Approaches PDGFR Inhibitor (Pan) PDGFR-alpha Inhibitor Avapritinib

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
PDGFRA D842V gastrointestinal stromal tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Phase Ib/II Actionable In a Phase I/II trial, treatment with Crenolanib (CP-868596) resulted in a clinical benefit rate of 31% (5/16) in gastronintestinal stromal tumor patients harboring PDGFRA D842V, with partial response in 2/16 and stable disease in 3/16 patients (J Clin Oncol 34, 2016 (suppl; abstr 11010)). detail...
PDGFRA D842V gastrointestinal stromal tumor resistant PDGFR Inhibitor (Pan) Imatinib Guideline Actionable Gleevec (imatinib) is not indicated for use in gastrointestinal stromal tumor (GIST) patients with PDGFRA D842V mutations (NCCN.org). detail...
PDGFRA D842V gastrointestinal stromal tumor predicted - sensitive PDGFR Inhibitor (Pan) Regorafenib Clinical Study - Cohort Actionable In a clinical study, Stivarga (regorafenib) treatment resulted in partial response in 11% (2/18) of patients and stable disease in 39% (7/18) of gastrointestinal stromal tumor patients, including prolonged stable disease for 12 months in a patient harboring PDGFRA D842V (PMID: 25905001). 25905001
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Imatinib Preclinical Actionable In a preclinical study, expression of PDGFRA D842V conferred resistance to Gleevec (imatinib) in cell culture (PMID: 15928335). 15928335
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Nilotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing PDGFRA D842V demonstrated resistance to growth inhibition by Tasigna (nilotinib) in culture (PMID: 18794084). 18794084
PDGFRA D842V gastrointestinal stromal tumor sensitive PDGFR Inhibitor (Pan) Dasatinib Phase 0 Actionable In a clinical trial, Sprycel (dasatinib) treatment resulted in a partial response in 25% (12/48) of patients with Gleevec (imatinib)-resistant gastrointestinal stromal tumor, with decreased tumor size in 2 of those patients, 1 of which harbored PDGFRA D842V (PMID: 29710216). 29710216
PDGFRA D842V gastrointestinal stromal tumor sensitive PDGFR Inhibitor (Pan) Dasatinib Guideline Actionable Sprycel (dasatinib) is included in the guidelines for patients with gastrointestinal stromal tumor (GIST) with PDGFRA D842V mutations (NCCN.org). detail...
PDGFRA D842V Advanced Solid Tumor resistant PDGFR Inhibitor (Pan) Sunitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing PDGFRA D842V demonstrated resistance to inhibition of PDGFRA phosphorylation by Sutent (sunitinib) in culture (PMID: 18955458). 18955458
PDGFRA D842V Advanced Solid Tumor sensitive PDGFR Inhibitor (Pan) Crenolanib Preclinical - Cell culture Actionable In a preclinical study, Crenolanib inhibited Pdgfra phosphorylation and proliferation of transformed cells expressing PDGFRA D842V in culture (PMID: 22745105). 22745105
PDGFRA D842V gastrointestinal stromal tumor sensitive Avapritinib PDGFR-alpha Inhibitor Avapritinib Phase I Actionable In a Phase I trial, BLU-285 treatment resulted in partial response lasted for more than 15 cycles of treatment, and sustained reduction of plasma PDGFRA D842V in a patient with gastrointestinal stromal tumor harboring PDGFRA D842V, whose disease had progressed on previous Gleevec (imatinib mesylate), Sprycel (dasatinib), and Crenolanib treatment (PMID: 29093181; NCT02508532). 29093181
PDGFRA D842V Advanced Solid Tumor sensitive Avapritinib PDGFR-alpha Inhibitor Avapritinib Preclinical - Cell culture Actionable In a preclinical study, BLU-285 inhibited Kit phosphorylation in transformed cells overexpressing PDGFRA D842V in culture (PMID: 29093181). 29093181
Clinical Trial Phase Therapies Title Recruitment Status
NCT02847429 Phase III Crenolanib Randomized Trial of Crenolanib in Subjects With D842V Mutated GIST Recruiting