A phase Ib/II study of MEK162 (binimetinib [BINI]) in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST).

10507 Background: ETV1, a lineage-specific survival factor for GIST and its precursor interstitial cells of Cajal, represents a promising therapeutic target in GIST. In preclinical models, MEK inhibition with BINI, synergizes with imatinib in destabilizing ETV1 protein and suppressing GIST tumorigenesis and progression. Combined MEK and KIT inhibition therefore represents a novel therapeutic approach for patients with GIST. Methods: The phase Ib portion of the imatinib (400 mg daily) plus BINI was performed in patients (pts) with imatinib-resistant advanced GIST. A standard 3+3 dosing schema was utilized to determine the recommended phase II dose (RP2D) of this combination. Additional pts were enrolled on an expansion cohort at the RP2D. Responses were assessed by RECIST1.1 and Choi criteria every 8 weeks. Custom targeted next-generation sequencing with the Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) was performed on archived tumor samples for all pts. Results: Eighteen pts enrolle...