{"entity":{"id":"paper-checkmate-227-n-engl-j-med-2018","kind":"paper","name":"Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden","aka":[],"tldr":"Published report from the CheckMate 227 trial registered as NCT02477826, in New England Journal of Medicine (2018), chosen as the most cited paper whose own text cites the registry id.","summary":"Background: Nivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase).\n\nMethods: We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy. Those with a level of tumor programmed death ligand 1 (PD-L1) expression of at least 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy; those with a tumor PD-L1 expression level of less than 1% were randomly assigned, in a 1:1:1 ratio, to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Tumor mutational burden was determined by the FoundationOne CDx assay.\n\nResults: Progression-free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy. The 1-year progression-free survival rate was 42.6% with nivolumab plus ipilimumab versus 13.2% with chemotherapy, and the median progression-free survival was 7.2 months (95% confidence interval [CI], 5.5 to 13.2) versus 5.5 months (95% CI, 4.4 to 5.8) (hazard ratio for disease progression or death, 0.58; 97.5% CI, 0.41 to 0.81; P<0.001). The objective response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy. The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups, including patients with a PD-L1 expression level of at least 1% and those with a level of less than 1%. The rate of grade 3 or 4 treatment-related adverse events was 31.2% with nivolumab plus ipilimumab and 36.1% with chemotherapy. ical; CheckMate 227 ClinicalTrials.gov number, NCT02477826.).\n\nConclusions: Progression-free survival was significantly longer with first-line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden, irrespective of PD-L1 expression level. The results validate the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection. (Funded by Bristol-Myers Squibb and Ono Pharmaceut\n\nIndexed on Europe PMC as PubMed record 29658845 (DOI 10.1056/nejmoa1801946). Its abstract cites the registry id NCT02477826, 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 2018","url":"https://doi.org/10.1056/nejmoa1801946"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/29658845/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/29658845"},{"label":"ClinicalTrials.gov NCT02477826","url":"https://clinicaltrials.gov/study/NCT02477826"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-227"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2018,"doi":"10.1056/nejmoa1801946","pmid":"29658845","authors":"Hellmann MD, Ciuleanu TE, Pluzanski A, et al.","paperType":"rct","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02477826 with the most citations, so it is the natural first reading for anyone following the CheckMate 227 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-checkmate-227-n-engl-j-med-2018/","neighbours":{"trial":[{"id":"checkmate-227","kind":"trial","name":"CheckMate 227","route":"/trials/checkmate-227/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}