Intracranial Activity of Selpercatinib in Chinese Patients With Advanced RET Fusion–Positive Non–Small-Cell Lung Cancer in the Phase II LIBRETTO-321 Trial

PURPOSE: Selpercatinib, a highly selective, potent RET inhibitor with CNS activity, demonstrated sustained antitumor responses and intracranial activity in patients with RET-altered advanced non–small-cell lung cancer (NSCLC) in the global LIBRETTO-001 and Chinese LIBRETTO-321 trials. We report a prospective case series based on updated data from patients with brain metastases at baseline in LIBRETTO-321. MATERIALS AND METHODS: We included patients with advanced NSCLC and brain metastasis with a centrally confirmed KIF5B/CCDC6/NCOA4-RET fusion. Patients with previously treated or untreated CNS metastases were included if asymptomatic or neurologically stable. Patients received oral selpercatinib 160 mg, twice daily, until progression. Objective systemic and intracranial response was independently assessed per RECIST v1.1. The data cutoff (DCO) was March 31, 2022. RESULTS: In total, 8/26 (31%) patients were included: 1/8 (13%) had previous brain surgery but no previous systemic therapy and 3/8 (38%) had received brain radiotherapy. Best overall systemic response was partial response (PR) in 6/8 patients (75%) and stable disease (SD) in 2/8 (25%). Among patients with measurable baseline CNS lesions, 4/5 (80%) achieved a confirmed intracranial response (3/5 PRs and 1/5 complete response [CR]). The best overall intracranial response was CR in 3/8 (38%), PR in 3/8 (38%), and SD in 1/8 (13%) and nonprogressive disease/non-CR in 1/8 (13%); 2/8 patients (25%) had CNS-only disease progression. The duration of treatment was 2.8-24.0 months, and 5/8 patients (63%) had treatment ongoing at DCO. Of 8 patients, 5 (63%) had grade ≥3 treatment-related adverse events (TRAEs) requiring dose modification. There were no treatment discontinuations because of TRAEs. CONCLUSION: Selpercatinib demonstrated clinically meaningful and durable intracranial activity in Chinese patients with brain metastases from RET-altered NSCLC, consistent with the global LIBRETTO-001 trial.