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)

Active, enrolled Phase 3 Last updated 28 August 2025

What this trial tests

Phase 3 trial testing Pembrolizumab in Urinary Bladder Cancer, Muscle-invasive in 595 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

24 July 2019

Primary endpoint
6 June 2025

15 December 2027

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	595
Start date	24 July 2019
Primary completion	6 June 2025
Estimated completion	15 December 2027
Sites	242 locations across Italy, Colombia, Japan, Malaysia, Ireland, Poland, South Korea, Philippines

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →
• Surgery (radical cystectomy (RC) plus Pelvic Lymph Node Dissection [PLND])
• Enfortumab Vedotin — full drug profile →

Conditions studied

• Urinary Bladder Cancer, Muscle-invasive — all drugs for Urinary Bladder Cancer, Muscle-invasive →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Urinary Bladder Cancer, Muscle-invasive. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma.
   Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, et al · · 2021 · cited 880× · PMID 33577729 · DOI 10.1056/nejmoa2035807
2. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial.
   Bellmunt J, Hussain M, Gschwend JE, Albers P, et al · · 2021 · cited 322× · PMID 33721560 · DOI 10.1016/s1470-2045(21)00004-8
3. Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer.
   Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, et al · · 2023 · cited 195× · PMID 36041086 · DOI 10.1200/jco.22.01643
4. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer.
   O'Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, et al · · 2023 · cited 149× · PMID 37369081 · DOI 10.1200/jco.22.02887
5. The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors.
   Wei Q, Li P, Yang T, Zhu J, et al · · 2024 · cited 102× · PMID 38178200 · DOI 10.1186/s13045-023-01509-2
6. Mechanisms of Resistance to Antibody-Drug Conjugates.
   Khoury R, Saleh K, Khalife N, Saleh M, et al · · 2023 · cited 100× · PMID 37298631 · DOI 10.3390/ijms24119674
7. Biomaterials from the sea: Future building blocks for biomedical applications.
   Wan MC, Qin W, Lei C, Li QH, et al · · 2021 · cited 69× · PMID 33997505 · DOI 10.1016/j.bioactmat.2021.04.028
8. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3.
   Grivas P, Pouessel D, Park CH, Barthelemy P, et al · · 2024 · cited 66× · PMID 38261969 · DOI 10.1200/jco.22.02835