Taletrectinib (CNS-penetrant ROS1 TKI) delivers 55.8% ORR and 9.7-mo mPFS after prior ROS1 TKI

Taletrectinib (Ibtrozi) is an oral, next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor evaluated in pooled Phase 2 TRUST-I (NCT04395677; prior crizotinib) and TRUST-II (NCT04919811; prior crizotinib or entrectinib) in TKI-pretreated ROS1+ locally advanced/metastatic NSCLC (n=113 efficacy-evaluable; data cutoff Aug 31, 2025; median follow-up 35.8 months). Confirmed ORR was 55.8% (95% CI 46.1-65.1), median DOR 16.6 months, median PFS 9.7 months, and median OS 29.8 months; activity was maintained in key resistance/clinical subsets including ROS1 G2032R (ORR 61.5%, 8/13) and measurable CNS disease (intracranial ORR 65.6%). Safety (pooled across Phase 1/2; n=363) was described as similar to prior reports, but this abstract update does not provide updated Grade 3+ AE/discontinuation rates—so cross-trial tolerability comparisons vs other ROS1 TKIs (e.g., repotrectinib post-TKI) can’t be made from these data alone.