NCT03924895

Perioperative Pembrolizumab (MK-3475) Plus Cystectomy or Perioperative Pembrolizumab Plus Enfortumab Vedotin Plus Cystectomy Versus Cystectomy Alone in Participants Who Are Cisplatin-ineligible or Decline Cisplatin With Muscle-invasive Bladder Cancer (MK-3475-905/KEYNOTE-905/EV-303)

A Randomized Phase 3 Study Evaluating Cystectomy With Perioperative Pembrolizumab and Cystectomy With Perioperative Enfortumab Vedotin and Pembrolizumab Versus Cystectomy Alone in Participants Who Are Cisplatin-Ineligible or Decline Cisplatin With Muscle-Invasive Bladder Cancer (KEYNOTE-905/EV-303)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 595 (actual)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a study of perioperative pembrolizumab or enfortumab vedotin in combination with pembrolizumab in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that perioperative pembrolizumab plus radical cystectomy (RC) plus pelvic lymph node dissection (PLND) and perioperative enfortumab vedotin in combination with pembrolizumab plus RC+PLND will achieve superior event-free survival (EFS) compared with RC+PLND alone. With Amendment 5, outcome measures for programmed cell death ligand 1 (PD-L1) combined positive score (CPS) were removed. With Amendment 8, the primary outcome measure of pathologic complete response (pCR) rates was changed to a secondary outcome measure.

Conditions

• Urinary Bladder Cancer, Muscle-invasive

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Pembrolizumab 200 mg by intravenous (IV) infusion, given on Day 1 of each 21-day cycle.
PROCEDURE	Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])	Surgical RC+PLND will be done in accordance with the American Urological Association (AUA)/American Society of Clinical Oncology (ASCO)/American Society for Radiation Oncology (ASTRO)/Society of Urologic Oncology (SUO) guidelines.
DRUG	Enfortumab Vedotin	Enfortumab vedotin 1.25 mg/kg by intravenous (IV) infusion, given on Days 1 and 8 of each 21-day cycle.

Timeline

• Start date: 2019-07-24
• Primary completion: 2025-06-06
• Completion: 2027-12-15
• First posted: 2019-04-23
• Last updated: 2025-08-28

Locations

242 sites across 28 countries: United States, Argentina, Australia, Belgium, Canada, Colombia, Denmark, France, Germany, Hungary, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Thailand, Turkey (Türkiye), Ukraine, United Kingdom

Regulatory

• FDA-regulated drug study