Presentation (CTI)

OBJECTIVES: We compared taletrectinib, a highly potent, next-generation, selective central nervous system (CNS)-active ROS1-positive (ROS1+) tyrosine kinase inhibitor (TKI), with entrectinib, a TKI with perceived CNS activity. In the absence of head-to-head trials, our analysis utilized a matching-adjusted indirect comparison (MAIC) to focus on TKI-naive patients with ROS1+ non-small cell lung cancer (NSCLC).
METHODS: Pooled patient data for taletrectinib were obtained from the TRUST-I (NCT04395677) and TRUST-II (NCT04919811) studies, with a data cutoff of June 2024. These patients were matched to patients receiving entrectinib in the ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267) studies on gender, ECOG status, smoking history, histological classification, baseline CNS disease, and number of previous systemic therapies. Objective response rate (ORR), duration of response (DOR), and progression-free survival (PFS) were evaluated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using adjusted Cox regression models.
RESULTS: The covariates were balanced between the taletrectinib and entrectinib groups after matching. The ORR was significantly higher for taletrectinib (N=89; 87.6% [95% CI: 79.0%-93.7%]) than for entrectinib (N=161; 67.1% [95% CI: 59.2%-74.3%]) as the 95% CIs did not overlap. The HRs for DOR demonstrated a significant improvement in the likelihood of maintaining a response with taletrectinib vs entrectinib (0.35 [95% CI: 0.208-0.598]). Patients treated with taletrectinib experienced a significant 58% reduction in the rate of disease progression vs those treated with entrectinib (HR for PFS: 0.42 [95% CI: 0.274-0.649]).
CONCLUSIONS: Taletrectinib showed significantly improved outcomes vs entrectinib in TKI-naive patients with ROS1+ NSCLC in the cross-trial MAIC analysis, including higher ORR and substantially reduced rate of progression. Additional analyses with more mature DOR and PFS data, along with a comparative analysis of safety outcomes, will provide a comprehensive benefit-risk assessment.