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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) | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

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

NCT05845814•Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
•* Participants with mixed histology are eligible provided the urothelial component is ≥50% (and \<10% plasmacytoid component)

Exclusion Criteria

•Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted:
•* Participants that received neoadjuvant or adjuvant chemotherapy are permitted.
•* Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence \>12 months from completion of therapy are permitted.
•Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.
•Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement or with \<Grade 2 neuropathy are eligible.
•Has a known additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
•Central nervous system (CNS) metastases are permitted on-study if all of the following are true: a) CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis; b) the participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment); c) participant does not have leptomeningeal disease.
•Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
•Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
+9 more criteria

Locations (47)

Moores Cancer Center ( Site 3028)

La Jolla, California, United States

University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 3045)

Orange, California, United States

UCSF Medical Center at Mission Bay ( Site 3044)

San Francisco, California, United States

Anschutz Cancer Pavilion ( Site 3017)

Aurora, Colorado, United States

Emory University School of Medicine ( Site 3043)

Atlanta, Georgia, United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 3011)

Indianapolis, Indiana, United States

Dana-Farber Cancer Institute ( Site 3047)

Boston, Massachusetts, United States

Siteman Cancer Center ( Site 3038)

St Louis, Missouri, United States

Icahn School of Medicine at Mount Sinai ( Site 3018)

New York, New York, United States

Memorial Sloan Kettering Cancer Center ( Site 3031)

New York, New York, United States

Key Dates

Start Date

June 23, 2023

Primary Completion Date

May 31, 2027

Completion Date

May 31, 2027

Last Updated

September 10, 2025

Enrollment

390

ESTIMATED participants

Conditions

Metastatic Urothelial CarcinomaUrothelial Neoplasms

Interventions

Coformulated favezelimab/pembrolizumab

BIOLOGICAL

Coformulated vibostolimab/pembrolizumab

BIOLOGICAL

COMBINATION_PRODUCT

Pembrolizumab

BIOLOGICAL

Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 10, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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)

Inclusion Criteria

Exclusion Criteria

Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

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