The DOI matches its Crossref record; 21 of the 22 references it cites were found in a registry or an index.
FDA Approval Summary: Sotorasib for KRAS G12C -Mutated Metastatic NSCLC
Open accessAbstract
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.
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“In 2021, the FDA approved sotorasib for the treatment of adult patients with KRAS G12C-mutated NSCLC, while adagrasib received similar approval the following year [48,50,51,52,53].”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [52]
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Cited by
Sorted by citations
Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies
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“By preventing KRAS signaling, sotorasib inhibits both in vitro and in vivo cell growth as well as tumor growth, and it only causes apoptosis in KRAS (G12C) tumor cell lines [68,72].”
BackgroundKRAS inhibitors: resistance drivers and combinatorial strategies
Isermann, T., Sers, C., Der, C. J., & Papke, B. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.11.009 · Cited by 217
Metadata
- Authors
- Nakajima, E. C., Drezner, N., Li, X., Mishra-Kalyani, P. S., Liu, Y., Zhao, H., Bi, Y., Liu, J., Rahman, A., Wearne, E., Ojofeitimi, I., Hotaki, L. T., Spillman, D., Pazdur, R., Beaver, J. A., & Singh, H.
- Affiliations
- United States Food and Drug Administration (US)
- Corresponding author
- Nakajima, Erica C.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2021-12-10
- Volume
- 28
- Issue
- 8
- Pages
- 1482-1486
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC9012672
- OpenAlex
- W4200034683
- Cited by
- 333
- References
- 22
- Citations by year
- 2026: 45 · 2025: 78 · 2024: 84 · 2023: 85 · 2022: 41
- FWCI
- 33.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- HHS | U.S. Food and Drug Administration
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- sotorasib, KRAS G12C mutation, metastatic non-small cell lung cancer, accelerated FDA approval, targeted therapy, overall response rate, adverse effects, hepatotoxicity, dose comparison
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Piperazines, Pyridines, Pyrimidines, Proto-Oncogene Proteins p21(ras), Clinical Trials, Phase I as Topic
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