RXDX-101, an oral Pan-Trk, ROS1, and ALK inhibitor, in patients with advanced solid tumors with relevant molecular alterations

摘要: Aim: RXDX-101 is a small molecule inhibitor of TrkA, TrkB, TrkC, ROS1 and ALK, with high potency and selectivity. RXDX-101 demonstrated potent pharmacological activity in preclinical studies and is potentially first-in-class against the Trk family of kinases. This study aims to determine MTD, PD, PK and anti-tumor activity in patients with advanced cancer and applicable molecular alterations.Methods: Phase 1 dose escalation in patients with advanced solid tumors. RXDX-101 was dosed orally once/day in a 4 day on, 3 day off schedule for 3 weeks, followed by a 7 day rest period, in continuous 28-day cycles. Minimum of 3 patients were enrolled at each dose level. Endpoints include safety, PK, and tumor response by RECIST.Results: 19 patients have been treated at 6 dose levels (100, 200, 400, 800,1200 and 1600 mg/m2). RXDX-101 has been well tolerated to date; the MTD has not been reached. No DLT has …