TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naïve and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD….Intracranial-ORR was 91.6%; ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naïve and CRZ-pretreated pts, respectively; mPFS was 33.2 mo and 9.8 mo....With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs.

Of 4 patients with ROS1 G2032R mutation, 3 patients achieved partial response (PR), and 1 patient achieved stable disease (SD)….Taletrectinib demonstrated meaningful clinical efficacy in both TKI-naïve and crizotinib-pretreated ROS1 positive NSCLC patients. In particular, taletrectinib showed clinical effectiveness in patients with ROS1 secondary G2032 mutations and patients with brain metastasis.