# EV-304 / KEYNOTE-B15

Source: https://onco.cc/trials/ev-304/  
OnCo record `ev-304` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Also known as: EV-304; KEYNOTE-B15
- Registry id: NCT04700124
- Phase: 3
- Setting: Cisplatin-eligible MIBC: perioperative enfortumab vedotin + pembrolizumab vs neoadjuvant gemcitabine-cisplatin, both with cystectomy
- Sponsor: Merck / Astellas / Pfizer
- Enrolled: 808
- Result: EFS, OS, and pCR significantly improved (topline; details pending).
- Outcomes: Event-free survival at 2 years: Perioperative enfortumab vedotin + pembrolizumab 79.4% vs Neoadjuvant cisplatin-gemcitabine 66.2%, HR 0.53; Overall survival at 2 years: Perioperative enfortumab vedotin + pembrolizumab 86.9% vs Neoadjuvant cisplatin-gemcitabine 81.3%, HR 0.65; Pathological complete response: Perioperative enfortumab vedotin + pembrolizumab 55.8% vs Neoadjuvant cisplatin-gemcitabine 32.5%
- 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.

## Sources

- ClinicalTrials.gov NCT04700124: https://clinicaltrials.gov/study/NCT04700124
- OncLive topline report: https://www.onclive.com/view/perioperative-enfortumab-vedotin-pembrolizumab-meets-efs-os-pcr-end-points-in-cisplatin-eligible-mibc

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- drugs: [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Astellas](https://onco.cc/companies/astellas/)
- pairings: [Enfortumab vedotin + pembrolizumab across the bladder cancer continuum](https://onco.cc/pairings/ev-pembro-continuum/)
- ideas: [Bladder preservation for MIBC after perioperative EV + pembrolizumab complete response](https://onco.cc/ideas/idea-bladder-preservation-mibc/)

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