Phase II trial of imatinib plus binimetinib for treatment-naive advanced gastrointestinal stromal tumor

Most patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib. Dual targeting or the GIST lineage-specific master regulators, ETV1 and KIT, by MEK and KIT inhibitors was active preclinically. A phase II study at Memorial Sloan Kettering Cancer Center (New York, NY) evaluated the combination of imatinib and binimetinib for previously untreated advanced GIST. The study met its primary end point with a best ORR of 69% (955 CI 52.9-82.4). The median PFS was 29.9 months (95% CI 24.2-NE) and the median OS was not reached (95% CI 50.4-NE). The toxicity was manageable.