Selpercatinib in Chinese patients with -fusion-positive non-small-cell lung cancer: updated efficacy and safety analysis from the randomized LIBRETTO-321 phase II trial.

Background: Selpercatinib is approved for the treatment of -fusion-positive non-small-cell lung cancer (NSCLC).

Objective: We present a final update on LIBRETTO-321 to enhance the understanding of long-term efficacy and safety in Chinese patients.

Design: This open-label, multicenter, phase II study included patients with advanced -altered solid tumors.

Methods: The primary endpoint was objective response rate (ORR), and Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was assessed by the independent review committee. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), central nervous system (CNS) response, and safety.

Results: A total of 47 patients (treatment-naïve ( = 11); pre-treated ( = 36)) with NSCLC were enrolled. The ORR in overall NSCLC was 72.3% (95% CI: 57.4, 84.4), treatment-naïve was 100.0% (95% CI: 71.5, 100.0); and pre-treated was 63.9% (95% CI: 46.2, 79.2). Median DOR was not reached for overall NSCLC, with 53% of responses ongoing at the data cutoff (median follow-up: 34.2 months). With a median follow-up of 35.9 months, the median PFS for overall NSCLC was 27.6 months (95% CI: 22.3, not evaluable (NE)), treatment-naïve was 27.6 months (95% CI: 16.4, NE), and pre-treated was 27.8 months (95% CI: 19.29, NE). The 3-year OS rate for overall NSCLC was 62.0% (95% CI: 45.9, 74.6) with a median follow-up of 38.1 months. Among five patients with measurable CNS metastases, four achieved intracranial responses. The safety profile was consistent with previous reports.

Conclusion: With additional follow-up, selpercatinib showed durable responses, prolonged survival, and a consistent safety profile in Chinese patients with -fusion-positive NSCLC.

Trial Registration: Clinical Trials.gov identifier (NCT04280081).