{"entity":{"id":"keynote-689","kind":"trial","name":"KEYNOTE-689","aka":[],"tldr":"The first new treatment for curable head and neck cancer in six years: immunotherapy around surgery doubled the time patients stayed free of events.","summary":"Presented AACR April 2025; FDA approval 12 June 2025 for PD-L1 CPS ≥1. In the CPS ≥1 population (n=682), median EFS 59.7 vs 29.6 months. Major pathological response in ~10% of the neoadjuvant arm predicted excellent outcomes. First perioperative approval in HNSCC and the first HNSCC approval since 2019.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03765918","url":"https://clinicaltrials.gov/study/NCT03765918"},{"label":"FDA approval, Merck","url":"https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-pd-l1-resectable-locally-advanced-head-neck-squamous-cell-carcinoma-as-neoadjuvant-treatment-continued-as-adjuvant-treatment-combined-with-radiother/"}],"tags":[],"related":[],"cancers":["head-and-neck","hpv-negative-head-and-neck-cancer"],"sections":[],"technologies":["imrt-igrt"],"targets":["pd1"],"drugs":["pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","efs","cps"],"trials":[],"people":["ravindra-uppaluri"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03765918","phase":"3","setting":"Resectable stage III-IVA HNSCC: neoadjuvant pembrolizumab, surgery, then adjuvant pembrolizumab with (chemo)radiation vs surgery and (chemo)radiation","sponsor":"Merck","result":"Median EFS 59.7 vs 29.6 months (CPS ≥1).","started":"2018-12-17","startedType":"actual","yearReported":2025,"enrolled":714,"enrolledBasis":"registry","outcomes":[{"endpoint":"Event-free survival (CPS ≥1)","primary":true,"unit":"months","arms":[{"name":"Perioperative pembrolizumab","n":682,"value":59.7},{"name":"Standard of care","value":29.6}],"source":"https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-pd-l1-resectable-locally-advanced-head-neck-squamous-cell-carcinoma-as-neoadjuvant-treatment-continued-as-adjuvant-treatment-combined-with-radiother/"}],"replication":"No second phase 3 yet; consistent with neoadjuvant IO benefits in melanoma and lung."},"route":"/trials/keynote-689/","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":"hypopharyngeal-cancer","kind":"cancer","name":"Hypopharyngeal cancer","route":"/cancers/hypopharyngeal-cancer/"},{"id":"oral-tongue-cancer","kind":"cancer","name":"Oral tongue and floor of mouth cancer","route":"/cancers/oral-tongue-cancer/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"target":[{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"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/"},{"id":"efs","kind":"term","name":"Event-free / disease-free survival (EFS, DFS, iDFS, RFS)","route":"/terms/efs/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"person":[{"id":"ravindra-uppaluri","kind":"person","name":"Ravindra Uppaluri","route":"/people/ravindra-uppaluri/"}],"pairing":[{"id":"io-before-surgery-hnscc","kind":"pairing","name":"Immunotherapy before surgery rather than with chemoradiation (HNSCC)","route":"/pairings/io-before-surgery-hnscc/"}],"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/"}],"paper":[{"id":"paper-keynote-689-nejm-2025","kind":"paper","name":"KEYNOTE-689: neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck cancer","route":"/key-papers/paper-keynote-689-nejm-2025/"}],"trial":[{"id":"nivopostop","kind":"trial","name":"NIVOPOSTOP (GORTEC 2018-01)","route":"/trials/nivopostop/"}]}}