Adagrasib: First Approval
Open accessAbstract
Adagrasib (KRAZATI™) is an orally available, potent, irreversible, small molecule inhibitor of KRAS G12C mutant isoform being developed by Mirati Therapeutics for the treatment of solid tumours harbouring KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Adagrasib covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state, thereby preventing downstream signalling without affecting wild-type KRAS protein. In December 2022, adagrasib received its first approval in the USA for the treatment of adults with KRAS G12C-mutated locally advanced or metastatic NSCLC (as determined by an FDA approved test) who have received ≥ 1 prior systemic therapy. It was approved under accelerated approval based on objective response rate and duration of response, and its continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s). The drug is under regulatory review for NSCLC in the European Union and is in development for CRC in the US. Clinical studies of adagrasib in solid tumours, including CRC, are underway in several countries. This article summarizes the milestones in the development of adagrasib leading to this first approval for KRAS G12C-mutated locally advanced or metastatic NSCLC.
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Sotorasib and adagrasib have been approved by the US FDA for locally advanced or metastatic non-small-cell lung cancer, but not for metastatic colorectal cancer as monotherapy as of the paper.
“In recent years, two KRAS G12C inhibitors, sotorasib and adagrasib, have been approved by the United States Food and Drug Administration (US FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC), 8,9 but not in mCRC as monotherapy as to date.”
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- Authors
- Dhillon, S.
- Affiliations
- Springer Nature (New Zealand) (NZ)
- Corresponding author
- Dhillon, Sohita
- Venue
- Drugs
- Published
- 2023-02
- Volume
- 83
- Issue
- 3
- Pages
- 275-285
- ISSN
- 0012-6667 (ISSN-L)
- 1179-1950
- OpenAlex
- W4319826818
- Semantic Scholar
- 57b9b485bca58786b3d6ba75596fdbe6e83f4991
- Cited by
- 161
- References
- 21
- Citations by year
- 2026: 39 · 2025: 52 · 2024: 50 · 2023: 20
- FWCI
- 7.45
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Drugs (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by-nc)
- Figshare
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- adagrasib, KRAS G12C inhibitors, non-small cell lung cancer, colorectal cancer, accelerated approval, FDA approval, drug development milestones, oncogenic KRAS mutations, small-molecule kinase inhibitors
- MeSH terms
- Acetonitriles, Adult, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mutation, Piperazines, Pyrimidines, Proto-Oncogene Proteins p21(ras)
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