A phase 1 study of the next-generation ALK/ROS1/TRK inhibitor ropotrectinib (TPX-0005) in patients with advanced ALK/ROS1/NTRK+ cancers (TRIDENT-1).

2513Background: Pts with ALK/ ROS1/NTRK fusion-positive cancers can develop on-target TKI resistance [e.g. solvent front mutations (SFMs)] and/or central nervous system (CNS) relapse. Ropotrectinib is a potent next-generation ALK/ ROS1/TRK TKI designed to inhibit SFMs in addition to most clinically relevant resistance mutations. Methods: Phase I eligible pts had ALK, ROS1, or NTRK1-3 fusion-positive advanced solid tumors and were TKI-naive or TKI pre-treated. Pts with treated/untreated asymptomatic brain mets were allowed. Dose escalation followed a 3+3 design. Results: As of Jan 2, 2018, 65 pts (28 ALK+, 29 ROS1+, and 8 NTRK+) received at least 1 dose of ropotrectinib. The most common tumor was NSCLC (83%). The median # of prior chemo- or immune-therapy was 1 (range 0-9). Many pts were TKI pre-treated (86% of ALK+ had ≥ 2 prior TKIs, 66% of ROS1+ and 50% of NTRK+ had ≥ 1 prior TKIs). 23 pts (35%) had baseline CNS metastases, including 52% with untreated CNS disease. Pts were treated over 5 dose levels/ sche...