{"entity":{"id":"ev-304","kind":"trial","name":"EV-304 / KEYNOTE-B15","aka":["EV-304","KEYNOTE-B15"],"tldr":"The trial that could replace chemotherapy before bladder removal in fit patients with an ADC plus immunotherapy.","summary":"EV-304, also KEYNOTE-B15, trial NCT04700124 sponsored by Merck, Astellas and Pfizer and reported from December 2025, is the trial that could replace chemotherapy before bladder removal in fit patients with an antibody-drug conjugate plus immunotherapy. It randomised 808 cisplatin-eligible patients with muscle-invasive bladder cancer to perioperative enfortumab vedotin plus pembrolizumab or neoadjuvant gemcitabine and cisplatin, both with cystectomy, and showed significant improvements in event-free survival, overall survival and pathologic complete response, published in the New England Journal of Medicine with a filing expected in 2026. Whether the pair becomes the default across the whole bladder cancer pathway is the question it and EV-302 together pose.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04700124","url":"https://clinicaltrials.gov/study/NCT04700124"},{"label":"OncLive topline report","url":"https://www.onclive.com/view/perioperative-enfortumab-vedotin-pembrolizumab-meets-efs-os-pcr-end-points-in-cisplatin-eligible-mibc"}],"tags":[],"related":[],"cancers":["urothelial"],"sections":[],"technologies":["adc"],"targets":[],"drugs":["enfortumab-vedotin","pembrolizumab"],"companies":["astellas"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04700124","phase":"3","setting":"Cisplatin-eligible MIBC: perioperative enfortumab vedotin + pembrolizumab vs neoadjuvant gemcitabine-cisplatin, both with cystectomy","sponsor":"Merck / Astellas / Pfizer","result":"EFS, OS, and pCR significantly improved (topline; details pending).","started":"2021-04-21","startedType":"actual","yearReported":2025,"enrolled":808,"enrolledBasis":"registry","outcomes":[{"endpoint":"Event-free survival at 2 years","primary":true,"unit":"%","arms":[{"name":"Perioperative enfortumab vedotin + pembrolizumab","n":405,"value":79.4},{"name":"Neoadjuvant cisplatin-gemcitabine","n":403,"value":66.2}],"hr":0.53,"ci":[0.41,0.7],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2601486"},{"endpoint":"Overall survival at 2 years","unit":"%","arms":[{"name":"Perioperative enfortumab vedotin + pembrolizumab","value":86.9},{"name":"Neoadjuvant cisplatin-gemcitabine","value":81.3}],"hr":0.65,"ci":[0.48,0.89],"p":"0.006","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2601486"},{"endpoint":"Pathological complete response","unit":"%","arms":[{"name":"Perioperative enfortumab vedotin + pembrolizumab","value":55.8},{"name":"Neoadjuvant cisplatin-gemcitabine","value":32.5}],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2601486"}],"replication":"Mirrors EV-303/KEYNOTE-905 in cisplatin-ineligible MIBC (same regimen, EFS and OS benefit), so the perioperative EV + pembrolizumab effect has now been shown in two randomised populations."},"route":"/trials/ev-304/","neighbours":{"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"}],"technology":[{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"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/"}],"pairing":[{"id":"ev-pembro-continuum","kind":"pairing","name":"Enfortumab vedotin + pembrolizumab across the bladder cancer continuum","route":"/pairings/ev-pembro-continuum/"}],"idea":[{"id":"idea-bladder-preservation-mibc","kind":"idea","name":"Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response","route":"/ideas/idea-bladder-preservation-mibc/"}]}}