# Enfortumab vedotin + pembrolizumab across the bladder cancer continuum

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

## TL;DR

The ADC-immunotherapy pair that doubled survival in advanced disease now also works around surgery, in fit and unfit patients alike.

## Summary

Enfortumab vedotin, a Nectin-4-directed antibody-drug conjugate, combined with pembrolizumab is the first regimen to displace platinum chemotherapy at every stage of a common solid tumour, bladder and urothelial cancer. Nectin-4 is expressed on almost all urothelial cancers, and the MMAE payload induces immunogenic cell death and dendritic-cell maturation that the PD-1 antibody then exploits. Three positive phase 3 trials underpin it: EV-302 / KEYNOTE-A39 in metastatic disease, where survival improved substantially over chemotherapy, EV-303 / KEYNOTE-905 in cisplatin-ineligible muscle-invasive disease, approved in November 2025, and EV-304 / KEYNOTE-B15 in cisplatin-eligible disease, positive in December 2025. The pairing now serves fit and unfit patients alike.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Enfortumab vedotin + Pembrolizumab
- Type: combination
- Rationale: Nectin-4 is near-universal in urothelial cancer; MMAE induces immunogenic cell death and dendritic-cell maturation that pembrolizumab exploits.
- Evidence: Three positive phase 3 trials.

## Sources

- ClinicalTrials.gov NCT04223856: EV-302 / KEYNOTE-A39: https://clinicaltrials.gov/study/NCT04223856
- ClinicalTrials.gov NCT03924895: EV-303 / KEYNOTE-905: https://clinicaltrials.gov/study/NCT03924895

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/)
- drugs: [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- trials: [EV-302 / KEYNOTE-A39](https://onco.cc/trials/ev-302/), [EV-303 / KEYNOTE-905](https://onco.cc/trials/ev-303/), [EV-304 / KEYNOTE-B15](https://onco.cc/trials/ev-304/)

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