{"entity":{"id":"ev-302","kind":"trial","name":"EV-302 / KEYNOTE-A39","aka":["EV-302","KEYNOTE-A39"],"tldr":"Nearly doubled survival in advanced bladder cancer, ending 40 years of platinum chemotherapy as the standard.","summary":"EV-302, also KEYNOTE-A39, trial NCT04223856 sponsored by Astellas, Pfizer and Merck and published in the New England Journal of Medicine in 2023, nearly doubled survival in first-line advanced urothelial cancer, ending forty years of platinum chemotherapy as the standard. It randomised 886 patients to enfortumab vedotin plus pembrolizumab or platinum with gemcitabine, met both primary endpoints of progression-free and overall survival with very large effects and a much higher response rate, and the extended follow-up in 2025 maintained the survival advantage. It is the template for ADC plus immunotherapy combinations now copied in breast and lung cancer, and how far that template travels is the open question.","status":"positive","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT04223856","url":"https://clinicaltrials.gov/study/NCT04223856"}],"tags":[],"related":[],"cancers":["urothelial","muscle-invasive-bladder-cancer"],"sections":[],"technologies":["adc"],"targets":["nectin4"],"drugs":["enfortumab-vedotin","pembrolizumab"],"companies":["astellas"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["thomas-powles","jonathan-rosenberg","lee-jae-lyun"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04223856","phase":"3","setting":"First-line advanced urothelial cancer: enfortumab vedotin + pembrolizumab vs platinum chemotherapy","sponsor":"Astellas / Pfizer / Merck","result":"OS HR 0.47.","started":"2020-03-30","startedType":"actual","yearReported":2023,"enrolled":886,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Enfortumab vedotin + pembrolizumab","n":442,"value":12.5},{"name":"Platinum + gemcitabine","n":444,"value":6.3}],"hr":0.45,"ci":[0.38,0.54],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2312117"},{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Enfortumab vedotin + pembrolizumab","value":31.5},{"name":"Platinum + gemcitabine","value":16.1}],"hr":0.47,"ci":[0.38,0.58],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2312117"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Enfortumab vedotin + pembrolizumab","value":67.7},{"name":"Platinum + gemcitabine","value":44.4}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2312117"}],"replication":"Confirms EV-103 (phase 1b/2, ORR 68%); the extended follow-up in 2025 maintained the OS hazard ratio."},"route":"/trials/ev-302/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"muscle-invasive-bladder-cancer","kind":"cancer","name":"Muscle-invasive and advanced bladder cancer","route":"/cancers/muscle-invasive-bladder-cancer/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"nectin4","kind":"target","name":"Nectin-4","route":"/targets/nectin4/"}],"drug":[{"id":"enfortumab-vedotin","kind":"drug","name":"Enfortumab vedotin","route":"/drugs/enfortumab-vedotin/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"astellas","kind":"company","name":"Astellas","route":"/companies/astellas/"}],"person":[{"id":"lee-jae-lyun","kind":"person","name":"Jae Lyun Lee","route":"/people/lee-jae-lyun/"},{"id":"jonathan-rosenberg","kind":"person","name":"Jonathan E. Rosenberg","route":"/people/jonathan-rosenberg/"},{"id":"thomas-powles","kind":"person","name":"Thomas Powles","route":"/people/thomas-powles/"}],"pairing":[{"id":"adc-plus-io","kind":"pairing","name":"ADC + checkpoint inhibitor","route":"/pairings/adc-plus-io/"},{"id":"ev-pembro-continuum","kind":"pairing","name":"Enfortumab vedotin + pembrolizumab across the bladder cancer continuum","route":"/pairings/ev-pembro-continuum/"}],"roadmap":[{"id":"adc-generations","kind":"roadmap","name":"ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs","route":"/roadmaps/adc-generations/"},{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"}],"paper":[{"id":"paper-ev-302-nejm-2024","kind":"paper","name":"EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer","route":"/key-papers/paper-ev-302-nejm-2024/"}]}}