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KEYNOTE-905/EV-303

Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer

Phase 3N = 344NCT03924895

Population
Muscle-invasive bladder cancer, ineligible for or declining cisplatin-based chemotherapy (described in the abstract as a predominantly cisplatin-ineligible population)
Design
Phase 3, open-label randomised trial in muscle-invasive bladder cancer in participants ineligible for or declining cisplatin-based chemotherapy: perioperative enfortumab vedotin plus pembrolizumab and surgery (surgery after 3 cycles; 9 total cycles of enfortumab vedotin and 17 total cycles of pembrolizumab) versus surgery alone. Primary end point event-free survival; key secondary end points overall survival and pathological complete response. The ClinicalTrials.gov record (595 enrolled) also lists a third arm, pembrolizumab with surgery, which the abstract of this report does not describe; 344 participants were randomised to the two arms reported here.
Primary endpoint
EFS
Arms
  • Enfortumab vedotin plus pembrolizumab, then surgery (experimental, n = 170): Perioperative enfortumab vedotin 1.25 mg per kilogram on days 1 and 8 plus pembrolizumab 200 mg on day 1 every 3 weeks, with surgery after 3 cycles; 9 total cycles of enfortumab vedotin and 17 of pembrolizumab
  • Surgery alone (control, n = 174): Surgery alone (control)
People
Vulsteke C, senior author Ullén A, KEYNOTE-905/EV-303 Investigators
EFSHR 0.40 (95% CI 0.28–0.57)Δ 24-month EFS+35.3 pointsOSHR 0.50 (95% CI 0.33–0.74)Δ 24-month OS+16.6 pointsΔ pCR+48.5 points
Show the numbers
Results reported for KEYNOTE-905/EV-303
EndpointAnalysisEnfortumab vedotin plus pembrolizumab, then surgerySurgery aloneEffect
EFSRandomised patients (analysis population not stated in the abstract)primarymedian follow-up 25.6 monthsVulsteke 202674.7% at 2 y39.4% at 2 yHR 0.40 (95% CI 0.28–0.57)P<0.001 (two-sided)Median follow-up at data cutoff 25.6 months (range 11.8 to 53.7).
OSRandomised patients (analysis population not stated in the abstract)primaryVulsteke 202679.7% at 2 y63.1% at 2 yHR 0.50 (95% CI 0.33–0.74)P<0.001 (two-sided)Overall survival was a key secondary end point.
pCRRandomised patients (analysis population not stated in the abstract)Absence of viable tumour after surgical resection (the abstract's definition).primaryVulsteke 202657.1%8.6%P<0.001 (two-sided)Estimated difference 48.3 percentage points (95% CI 39.5 to 56.5). Key secondary end point.
Results reported for KEYNOTE-905/EV-303
EndpointAnalysisEnfortumab vedotin plus pembrolizumab, then surgerySurgery aloneEffect
EFSRandomised patients (analysis population not stated in the abstract)primarymedian follow-up 25.6 monthsVulsteke 202674.7% at 2 y39.4% at 2 yHR 0.40 (95% CI 0.28–0.57)P<0.001 (two-sided)Median follow-up at data cutoff 25.6 months (range 11.8 to 53.7).
OSRandomised patients (analysis population not stated in the abstract)primaryVulsteke 202679.7% at 2 y63.1% at 2 yHR 0.50 (95% CI 0.33–0.74)P<0.001 (two-sided)Overall survival was a key secondary end point.
pCRRandomised patients (analysis population not stated in the abstract)Absence of viable tumour after surgical resection (the abstract's definition).primaryVulsteke 202657.1%8.6%P<0.001 (two-sided)Estimated difference 48.3 percentage points (95% CI 39.5 to 56.5). Key secondary end point.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
EFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
EFS0.40.28–0.57
OS0.50.33–0.74
Primary publication: Vulsteke C, Adra N, Danchaivijitr P, Sabadash M, Rodriguez-Vida A, Zhang Z, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026;394(13):1257-1269. PubMedDOI

Appears in

Sources

  1. Vulsteke C, Adra N, Danchaivijitr P, Sabadash M, Rodriguez-Vida A, Zhang Z, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026;394(13):1257-1269.

    PubMedDOI