FDA Approval Summary: Selpercatinib for the Treatment of Lung and Thyroid cancers with RET Gene Mutations or Fusions

Abstract

On May 8, 2020, the Food and Drug Administration granted accelerated approval to selpercatinib for 1) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), 2) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, and 3) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Approval was granted based on the clinically important effects on overall response rate (ORR) with prolonged duration of responses observed in a multicenter, open-label, multi-cohort clinical trial (LIBRETTO-001, NCT03157128) in patients whose tumors had RET alterations. ORRs within the approved patient populations ranged from 64% (95% CI: 54, 73) in prior platinum treated RET fusion-positive NSCLC to 100% (95% CI: 63, 100) in systemic therapy naïve RET fusion-positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. The product label includes warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. This is the first approval of a drug specifically for patients with RET alterations globally.