{"entity":{"id":"paper-keynote-001-pembrolizumab-nsclc-nejm-2015","kind":"paper","name":"KEYNOTE-001 (Garon 2015): pembrolizumab in non-small-cell lung cancer and the 50% PD-L1 cut-off","aka":[],"tldr":"The large early trial that showed pembrolizumab shrinks about a fifth of advanced lung cancers, with responses that last, and that identified a PD-L1 score of 50% or more as the group most likely to benefit.","summary":"KEYNOTE-001 treated 495 patients with advanced non-small-cell lung cancer, both previously treated and untreated, with pembrolizumab at several doses and schedules. The overall response rate was about 19% with a median duration of response around a year and no clear difference between doses. A training and validation approach on PD-L1 immunohistochemistry defined a tumour proportion score of at least 50% as the threshold at which response and survival were markedly better, a cut-off adopted by KEYNOTE-024 and now used in clinics worldwide.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1501824"},{"label":"ClinicalTrials.gov NCT01295827","url":"https://clinicaltrials.gov/study/NCT01295827"}],"tags":[],"related":["paper-keynote-024-nejm-2016","paper-keynote-010-lancet-2016"],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["pd1","pdl1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["tps","pd-l1-testing","orr"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2015,"doi":"10.1056/NEJMoa1501824","authors":"Garon EB, Rizvi NA, Hui R, et al.","paperType":"translational","findings":["495 patients with advanced NSCLC treated with pembrolizumab at 2 or 10 mg/kg every three weeks or 10 mg/kg every two weeks.","Objective response rate 19.4% overall; median duration of response 12.5 months.","PD-L1 tumour proportion score of at least 50%, seen in 23.2% of patients, was associated with a response rate of 45.2% and longer progression-free and overall survival.","Treatment-related grade 3 or higher adverse events in 9.5% of patients."],"whatItMeans":"This trial gave lung cancer its immunotherapy biomarker. The 50% PD-L1 cut-off decides today whether a patient with advanced lung cancer can start immunotherapy alone or needs chemotherapy added, and the five-year follow-up later showed long-term survivors among first-line responders.","caveats":["Single-arm study with several dose cohorts; the cut-off was derived and validated within the same trial.","PD-L1 testing depends on the assay and the sample and misses some responders."],"changedPractice":true,"participants":495},"route":"/key-papers/paper-keynote-001-pembrolizumab-nsclc-nejm-2015/","neighbours":{"paper":[{"id":"paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020","kind":"paper","name":"Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC","route":"/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/"},{"id":"paper-keynote-010-lancet-2016","kind":"paper","name":"KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer","route":"/key-papers/paper-keynote-010-lancet-2016/"},{"id":"paper-keynote-024-nejm-2016","kind":"paper","name":"KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer","route":"/key-papers/paper-keynote-024-nejm-2016/"}],"cancer":[{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pdl1-high-nsclc","kind":"cancer","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","route":"/cancers/pdl1-high-nsclc/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"pd-l1-testing","kind":"term","name":"PD-L1 expression testing (22C3, SP142, SP263)","route":"/terms/pd-l1-testing/"},{"id":"tps","kind":"term","name":"Tumour proportion score (TPS)","route":"/terms/tps/"}],"roadmap":[{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}]}}