Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jan;21(1):63-71.
doi: 10.1080/14796694.2024.2430172. Epub 2024 Nov 27.

Sotorasib for the treatment of locally advanced/metastatic non-small cell lung cancer

Jordyn P Higgins  1 , Jennifer W Carlisle  2 , Nader H Moniri  3   4 , Shruti Gupta  5 , Eziafa I Oduah  6 , Ticiana Leal  2
Affiliations
Review

Sotorasib for the treatment of locally advanced/metastatic non-small cell lung cancer

Jordyn P Higgins et al. Future Oncol. 2025 Jan.

Abstract

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is prognostic of poor survival for patients with non-small cell lung cancer (NSCLC). KRAS G12C mutations occur in 13% of NSCLC cases and despite the frequency of this mutation, advances in drug development against KRAS have historically been impeded due to the extremely high affinity of KRAS for guanosine triphosphate (GTP) and the lack of a binding pocket on the surface of KRAS that is suitable for drug binding. Sotorasib, a first-in-class, highly selective KRAS G12C inhibitor overcomes this issue by irreversibly binding in the switch-II pocket. Sotorasib was granted accelerated FDA approval for the treatment of KRASG12C-mutated locally advanced/metastatic NSCLC who have received at least one prior systemic therapy. This review summarizes the pharmacology, clinical efficacy, adverse effects, and clinical considerations of sotorasib.

Keywords: KRAS inhibitor; NSCLC; lung cancer; sotorasib; targeted therapy.

Plain language summary

Sotorasib is an oral targeted therapy option for the treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutations. KRAS G12C is a mutation of the KRAS protein that leads to uncontrollable cell growth of the cancer cells. This mutation is present in 13% of patients with NSCLC. Even though this mutation occurs frequently, it has taken some time for a drug to be developed that can target this mutation due to the unusual shape of KRAS G12C and a lack of suitable sites on it for drugs to attach. The review describes how sotorasib works, summarizes the data from clinical trials supporting its use, and information for providers to consider when prescribing this medication.

PubMed Disclaimer

Conflict of interest statement

Jennifer W. Carlisle is on the Advisory Board for Sanofi; and receives institutional research funding from Amgen, AstraZeneca, Daiichi Sankyo, Parexel and Hutchmed. Nader H. Moniri is Co-founder of Channel Therapeutics, LLC; and is a consultant for Galt Pharmaceuticals; and Scientific Board of Advisors for Institute of Advanced Medical Research; and has received funding from NIH/NHLBI. Eziafa I. Oduah has received grant funding from Bristol Myers Squibb. Ticiana Leal is on the advisory board/consulting for Catalyst, OncoC4, Jazz Pharmaceuticals, Amgen, AstraZeneca, Pfizer, Regeneron, Janssen, Gilead, Genentech, Novartis, Novocure, Sanofi, Takeda, BMS and AbbVie. Jordyn Higgins is on the advisory board for OncoHost, Johnson and Johnson. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Similar articles

See all similar articles

References

    1. Lung and bronchus cancer — cancer stat facts [internet]. [cited 2022 May 5]. Available from: https://seer.cancer.gov/statfacts/html/lungb.html
    1. What is lung cancer? | types of lung cancer [Internet]. [cited 2022 May 5]. Available from: https://www.cancer.org/cancer/lung-cancer/about/what-is.html
    1. Benjamin DJ, Xu A, Lythgoe MP, et al. Cancer drug approvals that displaced existing standard-of-care therapies, 2016-2021. JAMA Netw Open. 2022;5(3):e222265. doi: 10.1001/jamanetworkopen.2022.2265 - DOI - PMC - PubMed
    1. Kristina Gregory N, Lisa Hang M, Aisner DL, et al. NCCN guidelines version 7.2024 non-small cell lung cancer. NCCN Guidelines [Internet]. 2024. [cited 2024 Aug 19]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
    1. Judd J, Karim NA, Khan H, et al. Characterization of KRAS mutation subtypes in non-small cell lung cancer. Mol Cancer Ther [Internet]. 2021. [cited 2023 Oct 3];20(12):2577–2584. doi: 10.1158/1535-7163.MCT-21-0201 - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources