FDA Approval Summary: Sotorasib for KRAS G12C -Mutated Metastatic NSCLC

• Published in: Clinical cancer research Vol. 28; no. 8; pp. 1482 - 1486
• Main Authors: Nakajima, Erica C., Drezner, Nicole, Li, Xiaoxue, Mishra-Kalyani, Pallavi S., Liu, Yajun, Zhao, Hong, Bi, Youwei, Liu, Jiang, Rahman, Atiqur, Wearne, Emily, Ojofeitimi, Idara, Hotaki, Lauren Tesh, Spillman, Dianne, Pazdur, Richard, Beaver, Julia A., Singh, Harpreet
• Format: Journal Article
• Language: English
• Published: United States 14.04.2022
• Subjects: Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Clinical Trials, Phase I as Topic; Humans; Lung Neoplasms - chemically induced; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Mutation; Piperazines - therapeutic use; Proto-Oncogene Proteins p21(ras) - genetics; Pyridines; Pyrimidines
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-21-3074

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.