{"entity":{"id":"keynote-048","kind":"trial","name":"KEYNOTE-048","aka":[],"tldr":"Made immunotherapy the first treatment for advanced head and neck cancer, alone for PD-L1-rich tumours and with chemotherapy for the rest.","summary":"Pembrolizumab monotherapy improved OS in CPS ≥20 (14.9 vs 10.7 months) and CPS ≥1 (12.3 vs 10.3); pembrolizumab-chemotherapy improved OS in the total population (13.0 vs 10.7). FDA approval June 2019. Five-year follow-up confirmed durable survival tails. Replaced the EXTREME regimen as first line after a decade.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02358031","url":"https://clinicaltrials.gov/study/NCT02358031"},{"label":"Lancet 2019","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32591-7/fulltext"}],"tags":[],"related":[],"cancers":["head-and-neck","oropharyngeal-cancer","laryngeal-cancer","oral-cavity-cancer","recurrent-metastatic-hnscc","hypopharyngeal-cancer","hpv-negative-head-and-neck-cancer"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["pd1","pdl1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["cps"],"trials":["extreme"],"people":["barbara-burtness"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02358031","phase":"3","setting":"Untreated recurrent or metastatic HNSCC: pembrolizumab alone, pembrolizumab + platinum/5-FU, or cetuximab + platinum/5-FU (EXTREME)","sponsor":"Merck","result":"OS 14.9 vs 10.7 months (CPS ≥20, monotherapy); 13.0 vs 10.7 (all, with chemotherapy).","started":"2015-03-19","startedType":"actual","yearReported":2019,"enrolled":882,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival, CPS ≥20, pembrolizumab monotherapy","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab","value":14.9},{"name":"Cetuximab + chemotherapy","value":10.7}],"hr":0.61,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32591-7/fulltext"},{"endpoint":"Overall survival, total population, pembrolizumab + chemotherapy","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy","value":13},{"name":"Cetuximab + chemotherapy","value":10.7}],"hr":0.77,"source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32591-7/fulltext"}],"replication":"CheckMate 141 (nivolumab, second line) showed the same direction; KEYNOTE-040 was borderline. Class effect of PD-1 blockade in HNSCC is consistent."},"route":"/trials/keynote-048/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hpv-negative-head-and-neck-cancer","kind":"cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","route":"/cancers/hpv-negative-head-and-neck-cancer/"},{"id":"hpv-positive-oropharyngeal-cancer","kind":"cancer","name":"HPV-positive oropharyngeal cancer","route":"/cancers/hpv-positive-oropharyngeal-cancer/"},{"id":"hypopharyngeal-cancer","kind":"cancer","name":"Hypopharyngeal cancer","route":"/cancers/hypopharyngeal-cancer/"},{"id":"laryngeal-cancer","kind":"cancer","name":"Laryngeal and hypopharyngeal cancer","route":"/cancers/laryngeal-cancer/"},{"id":"lip-cancer","kind":"cancer","name":"Lip cancer","route":"/cancers/lip-cancer/"},{"id":"oral-cavity-cancer","kind":"cancer","name":"Oral cavity cancer (mouth and tongue)","route":"/cancers/oral-cavity-cancer/"},{"id":"oral-tongue-cancer","kind":"cancer","name":"Oral tongue and floor of mouth cancer","route":"/cancers/oral-tongue-cancer/"},{"id":"oropharyngeal-cancer","kind":"cancer","name":"Oropharyngeal cancer (tonsil and base of tongue)","route":"/cancers/oropharyngeal-cancer/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"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":"cps","kind":"term","name":"Combined positive score (CPS)","route":"/terms/cps/"}],"trial":[{"id":"extreme","kind":"trial","name":"EXTREME","route":"/trials/extreme/"}],"person":[{"id":"barbara-burtness","kind":"person","name":"Barbara Burtness","route":"/people/barbara-burtness/"}],"idea":[{"id":"idea-photoimmunotherapy-plus-pd1","kind":"idea","name":"Photoimmunotherapy as an in situ vaccine with PD-1 blockade","route":"/ideas/idea-photoimmunotherapy-plus-pd1/"},{"id":"idea-cost-low-dose-immunotherapy-trials","kind":"idea","name":"Test one-tenth-dose immunotherapy where the full dose is unaffordable","route":"/ideas/idea-cost-low-dose-immunotherapy-trials/"}],"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}]}}