Taletrectinib (CNS-penetrant ROS1 TKI) posts ~90% ORR and ~46-mo mPFS in ROS1+ NSCLC first-line

Taletrectinib is an oral, next-generation, selective ROS1 tyrosine kinase inhibitor (TKI) with CNS activity; this pooled update of the single-arm Phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials analyzed TKI-naïve ROS1+ locally advanced/metastatic NSCLC with measurable disease by independent review (n=157) at a data cutoff of Aug 31, 2025 (median follow-up 35.5 months). Confirmed ORR was 89.8% (95% CI 84.0-94.1), intracranial ORR was 76.5% (95% CI 50.1-93.2), median DOR was 49.7 months (95% CI 38.6-NR), and median PFS was 46.1 months (95% CI 31.8-NR)—numerically well above historical first-line ROS1 TKI benchmarks like crizotinib (ORR ~72%, mPFS ~19 months) and entrectinib (ORR ~67%, mPFS ~16 months), where durability is typically closer to ~1–2 years rather than ~4 years. No new safety signals were reported; safety was consistent versus the broader pooled safety population across Phase 1/2 (n=363), but the abstract does not quantify grade ≥3 AEs, discontinuations, or ROS1 TKI class-specific toxicities in this update.