ANS03 (type II ROS1/TRK TKI) shows 54.5% ORR in heavily pretreated ROS1+ NSCLC, including L2086F activity

ANS03 is a next-generation oral type II tyrosine kinase inhibitor targeting ROS1 and TRK designed to cover key acquired resistance mutations (including solvent-front mutations and the ROS1 Cβ6 L2086F). In the ongoing Phase 1 dose-escalation trial (NCT06716138) in locally advanced/metastatic ROS1- or NTRK-altered solid tumors, 20 fusion-positive NSCLC patients were enrolled; among 18 efficacy-evaluable ROS1 fusion-positive cancers, ORR was 38.8% (7/18) overall and 54.5% (6/11) in patients who had received ≥2 prior systemic lines and ≥1 prior ROS1 TKI (including patients with 2–4 prior ROS1 TKIs; one confirmed PR in an L2086F case at 12 weeks, plus 2 PRs at first assessment in patients with ≥6 prior systemic lines and ≥4 prior TKIs). Safety looked mainly hepatic-lab driven (AST/ALT 80%, bilirubin 35%, LDH 35%), Grade ≥3 TRAEs occurred in 25%, and neurotoxicity was reported only as low-grade events in 15%—a potentially differentiating feature versus repotrectinib where neurologic AEs (e.g., dizziness/dysgeusia) are common and in TKI-pretreated ROS1+ NSCLC the confirmed ORR is ~37.5% with mPFS ~9 months (TRIDENT-1; cross-trial comparison). Take Home: If the low-grade-only neurotoxicity holds up and responses extend to difficult resistance like L2086F, ANS03 could become a pragmatic “post–multi-ROS1 TKI” option—but at n=11 in the key pretreated slice, it’s still early and we need durability, CNS readouts, and mutation-stratified response rates to know if it truly beats today’s best salvage benchmarks.