# EV-302 / KEYNOTE-A39

Source: https://onco.cc/trials/ev-302/  
OnCo record `ev-302` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Also known as: EV-302; KEYNOTE-A39
- Registry id: NCT04223856
- Phase: 3
- Setting: First-line advanced urothelial cancer: enfortumab vedotin + pembrolizumab vs platinum chemotherapy
- Sponsor: Astellas / Pfizer / Merck
- Enrolled: 886
- Result: OS HR 0.47.
- Outcomes: Progression-free survival (BICR): Enfortumab vedotin + pembrolizumab 12.5 months vs Platinum + gemcitabine 6.3 months, HR 0.45; Overall survival: Enfortumab vedotin + pembrolizumab 31.5 months vs Platinum + gemcitabine 16.1 months, HR 0.47; Objective response rate: Enfortumab vedotin + pembrolizumab 67.7% vs Platinum + gemcitabine 44.4%
- Replication: Confirms EV-103 (phase 1b/2, ORR 68%); the extended follow-up in 2025 maintained the OS hazard ratio.

## Sources

- ClinicalTrials.gov NCT04223856: https://clinicaltrials.gov/study/NCT04223856

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Muscle-invasive and advanced bladder cancer](https://onco.cc/cancers/muscle-invasive-bladder-cancer/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [Nectin-4](https://onco.cc/targets/nectin4/)
- drugs: [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Astellas](https://onco.cc/companies/astellas/)
- people: [Jae Lyun Lee](https://onco.cc/people/lee-jae-lyun/), [Jonathan E. Rosenberg](https://onco.cc/people/jonathan-rosenberg/), [Thomas Powles](https://onco.cc/people/thomas-powles/)
- pairings: [ADC + checkpoint inhibitor](https://onco.cc/pairings/adc-plus-io/), [Enfortumab vedotin + pembrolizumab across the bladder cancer continuum](https://onco.cc/pairings/ev-pembro-continuum/)
- roadmaps: [ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs](https://onco.cc/roadmaps/adc-generations/), [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/)
- key papers: [EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer](https://onco.cc/key-papers/paper-ev-302-nejm-2024/)

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