1373P Efficacy and safety of taletrectinib in patients (Pts) with ROS1+ non-small cell lung cancer (NSCLC): Interim analysis of global TRUST-II study

Taletrectinib, a next-generation, CNS-active, ROS1 TKI with selectivity over TRKB, demonstrated high overall and intracranial response rates, prolonged PFS, activity against G2032R, and was well tolerated in TRUST-I (NCT04395677). We report interim results of taletrectinib from the pivotal phase 2 trial, TRUST-II (NCT04919811), in advanced ROS1+ NSCLC pts from North America, Europe, and Asia. TRUST-II, a multicenter, open-label, single-arm study in pts with ROS1+ tumors, has 4 cohorts: 1) NSCLC: ROS1 TKI-naive, ≤1 line of chemotherapy (CT); 2) NSCLC: 1 prior ROS1 TKI, ≤1 line of CT; 3) NSCLC: ≥2 ROS1 TKIs, ≤1 line of CT; and 4) solid tumors including NSCLC if ineligible for cohorts 1-3: ≤3 ROS1 TKIs, ≤2 lines of CT. Eligible pts had ECOG PS 0–1 and could have asymptomatic or treated/controlled CNS involvement. All pts started taletrectinib at 600 mg QD. The primary endpoint is independent review committee (IRC)-assessed confirmed objective response rate (cORRIRC); other key endpoints include investigator-assessed cORR (cORRINV), disease control rate (DCR), time to treatment response (TTR), DoR, PFS, and safety. Interim efficacy results are from 18 pts in cohort 1 and 22 pts in cohort 2 with ≥2 disease assessments (39% and 59% of pts had brain metastases, respectively). cORRINV was 94% (17/18; 95% CI: 73, 100) in cohort 1 and 55% (12/22; 95% CI: 32, 76) in cohort 2; DCR was 100% and 91%, respectively. cORRIRC will be presented. In both cohorts, median TTR was 1.4 mo; median DoR was not reached. As of March 31, 2023, 72 pts were included in the safety population that received ≥1 dose of taletrectinib. Median duration of exposure was 3.7 mo. Overall, 90% had a treatment-emergent adverse event (TEAE), mostly grade 1–2. The most common TEAEs were increased ALT (61%) or AST (61%), and nausea (38%). No treatment-related AE (TRAE) led to discontinuation or death; 24% of pts had a TRAE leading to dose reduction. In this ongoing global pivotal phase 2 study, taletrectinib demonstrated robust and consistent clinical activity with TRUST-I, including high response rates and a tolerable safety profile in both TKI-naive and TKI-pretreated pts with ROS1+ NSCLC.