{"entity":{"id":"paper-kras-nsclc-n-engl-j-med-2021","kind":"paper","name":"Sotorasib for Lung Cancers with KRAS p.G12C Mutation","aka":[],"tldr":"Phase 2 or 3 results paper on KRAS in Non-small-cell lung cancer, in New England Journal of Medicine (2021), one of the most cited Europe PMC records with KRAS in its title.","summary":"Background: Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC).\n\nMethods: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with KRAS p.G12C-mutated advanced NSCLC previously treated with standard therapies. The primary end point was objective response (complete or partial response) according to independent central review. Key secondary end points included duration of response, disease control (defined as complete response, partial response, or stable disease), progression-free survival, overall survival, and safety. Exploratory biomarkers were evaluated for their association with response to sotorasib therapy.\n\nResults: Among the 126 enrolled patients, the majority (81.0%) had previously received both platinum-based chemotherapy and inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). According to central review, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), including in 4 (3.2%) who had a complete response and in 42 (33.9%) who had a partial response. The median duration of response was 11.1 months (95% CI, 6.9 to could not be evaluated). Disease control occurred in 100 patients (80.6%; 95% CI, 72.6 to 87.2). The median progression-free survival was 6.8 months (95% CI, 5.1 to 8.2), and the median overall survival was 12.5 months (95% CI, 10.0 to could not be evaluated). Treatment-related adverse events occurred in 88 of 126 patients (69.8%), including grade 3 events in 25 patients (19.8%) and a grade 4 event in 1 (0.8%). Responses were observed in subgroups defined according to PD-L1 expression, tumor mutational burden, and co-occurring mutations in STK11, KEAP1, or TP53.\n\nConclusions: In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C-mutated NSCLC. (Funded by Amgen and the National Institutes of Health; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).\n\nIndexed on Europe PMC as PubMed record 34096690 (DOI 10.1056/nejmoa2103695). Its title names KRAS and its text names Non-small-cell lung cancer; PubMed types it as a clinical trial report (Clinical Trial, Phase II, Research Support, Non-U.S. Gov't, research-article, Multicenter Study, Research Support, N.I.H., Extramural). It was matched automatically to the idea \"Turn a brake back on: drugs that reactivate the PP2A phosphatase\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2021","url":"https://doi.org/10.1056/nejmoa2103695"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/34096690/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/34096690"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2021,"doi":"10.1056/nejmoa2103695","pmid":"34096690","authors":"Skoulidis F, Li BT, Dy GK, et al.","paperType":"observational","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for KRAS in Non-small-cell lung cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by KRAS in the title and Non-small-cell lung cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-kras-nsclc-n-engl-j-med-2021/","neighbours":{"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"idea":[{"id":"idea-bio1-pp2a-activators","kind":"idea","name":"Turn a brake back on: drugs that reactivate the PP2A phosphatase","route":"/ideas/idea-bio1-pp2a-activators/"}]}}