Multinational phase 1-2 trial of selpercatinib in RET fusion-positive non-small cell lung cancer: final results of LIBRETTO-001

Selpercatinib is a brain-penetrant selective RET inhibitor. The multinational phase 1-2 LIBRETTO-001 trial evaluated selpercatinib for RET fusion-positive cancers. Final results in the NSCLC cohort have now been published. Among patients who had previously received platinum-based chemotherapy (n=247) the objective response rate was 62%, with duration of response 31.6 months, median progression-free survival 26.2 months, and median overall survival was 47.6 months. Among treatment-naïve patients (n=69) the ORR was 83%, median DoR 20.3 months, median PFS 22.0 months. and median OS not reached (median duration of follow-up 43 months). At the 3-year landmark estimate, 57% of the pretreated and 66% of the treatment-naïve patients were alive. Among 26 patients with measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-DoR of 9.4 months and a CNS-PFS of 11.0 months. There were no new safety signals. The authors conclude that selpercatinib continued to show durable responses and intracranial activity, with a manageable safety profile, in patients with RET fusion-positive NSCLC.