FDA Approval Summary: Sotorasib for <i>KRAS G12C</i> -Mutated Metastatic NSCLC
Erica C. Nakajima, Nicole Drezner, Xiaoxue Li, Pallavi S. Mishra‐Kalyani, Yajun Liu, Hong Zhao, Youwei Bi, Jiang Liu, Atiqur Rahman, Emily Wearne, Idara Ojofeitimi, Lauren Tesh Hotaki, Dianne Spillman, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Abstract
On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The approval was based on CodeBreaK 100 (Study 20170543), a dose-escalation and dose-expansion trial in patients with an advanced, KRAS G12C-mutated, solid tumor. The overall response rate (ORR) observed in patients with KRAS G12C-mutated NSCLC treated with sotorasib (n = 124) was 36% [95% confidence interval (CI), 28-45]. The median duration of response was 10.0 months (95% CI, 6.9-not estimable). The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. This is the first approval of a targeted therapy for KRAS G12C-mutated NSCLC. Because of pharmacokinetic data and ORRs of patient cohorts who took sotorasib at lower doses in the dose-escalation portion of CodeBreaK 100, a dose comparison study is being conducted as a post-marketing requirement.