{"entity":{"id":"paper-nct03785249-n-engl-j-med-2022","kind":"paper","name":"Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS G12C Mutation","aka":[],"tldr":"Published report from the Phase 1 trial registered as NCT03785249, in New England Journal of Medicine (2022), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Adagrasib, a KRAS G12C inhibitor, irreversibly and selectively binds KRAS G12C, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study.\n\nMethods: In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with KRAS G12C -mutated non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy and anti-programmed death 1 or programmed death ligand 1 therapy. The primary end point was objective response assessed by blinded independent central review. Secondary end points included the duration of response, progression-free survival, overall survival, and safety.\n\nResults: at October 15, 2021, a total of 116 patients with KRAS G12C -mutated NSCLC had been treated (median follow-up, 12.9 months); 98.3% had previously received both chemotherapy and immunotherapy. Of 112 patients with measurable disease at baseline, 48 (42.9%) had a confirmed objective response. The median duration of response was 8.5 months (95% confidence interval [CI], 6.2 to 13.8), and the median progression-free survival was 6.5 months (95% CI, 4.7 to 8.4). at January 15, 2022 (median follow-up, 15.6 months), the median overall survival was 12.6 months (95% CI, 9.2 to 19.2). Among 33 patients with previously treated, stable central nervous system metastases, the intracranial confirmed objective response rate was 33.3% (95% CI, 18.0 to 51.8). Treatment-related adverse events occurred in 97.4% of the patients - grade 1 or 2 in 52.6% and grade 3 or higher in 44.8% (including two grade 5 events) - and resulted in drug discontinuation in 6.9% of patients.\n\nConclusions: In patients with previously treated KRAS G12C -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati Therapeutics; ClinicalTrials.gov number, NCT03785249.).\n\nIndexed on Europe PMC as PubMed record 35658005 (DOI 10.1056/nejmoa2204619). Its abstract cites the registry id NCT03785249, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2022","url":"https://doi.org/10.1056/nejmoa2204619"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35658005/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35658005"},{"label":"ClinicalTrials.gov NCT03785249","url":"https://clinicaltrials.gov/study/NCT03785249"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct03785249"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/nejmoa2204619","pmid":"35658005","authors":"Jänne PA, Riely GJ, Gadgeel SM, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03785249 with the most citations, so it is the natural first reading for anyone following the Phase 1 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-nct03785249-n-engl-j-med-2022/","neighbours":{"trial":[{"id":"nct03785249","kind":"trial","name":"Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1","route":"/trials/nct03785249/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}