NCT05845814

A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)

A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 390 (estimated)
• Sponsor: Merck Sharp & Dohme LLC · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and safety of coformulated favezelimab/pembrolizumab plus EV and coformulated vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of the treatment arms under study.

Detailed description

The master study for this substudy is MK-3475-U04/KEYMAKER-U04. The master study will not be screening any participants and will not be registered. With Amendment 2, participants will discontinue treatment with coformulated vibostolimab/pembrolizumab (Arm B) and be transitioned to pembrolizumab only. Per protocol, no analysis of Part 2 primary or secondary outcome measures (including efficacy or safety) will occur since Part 2 of the study will no longer take place.

Conditions

• Metastatic Urothelial Carcinoma
• Urothelial Neoplasms

Interventions

Type	Name	Description
BIOLOGICAL	Coformulated favezelimab/pembrolizumab	Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion
BIOLOGICAL	Coformulated vibostolimab/pembrolizumab	Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion
COMBINATION_PRODUCT	EV	1.25 mg/kg IV infusion
BIOLOGICAL	Pembrolizumab	200 mg IV infusion

Timeline

• Start date: 2023-06-23
• Primary completion: 2027-05-31
• Completion: 2027-05-31
• First posted: 2023-05-06
• Last updated: 2025-09-10

Locations

47 sites across 12 countries: United States, Australia, Canada, Chile, France, Israel, Italy, Netherlands, South Korea, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study