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

Clin Cancer Res. 2022 Apr 14;28(8):1482-1486. 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.

MeSH terms

  • 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


  • KRAS protein, human
  • Piperazines
  • Pyridines
  • Pyrimidines
  • sotorasib
  • Proto-Oncogene Proteins p21(ras)