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NCT07232602PHASE1, PHASE2Recruiting

KEYMAKER-U04 Substudy 04D: A Clinical Study of New Treatments Given With Enfortumab Vedotin and Pembrolizumab in People With Urothelial Cancer (MK-3475-04D/KEYMAKER-U04)

Merck Sharp & Dohme LLC

Start Date

2/9/2026

Completion Date

7/8/2031

Summary

Researchers are looking for new ways to treat people with urothelial cancer (UC) that is locally advanced or metastatic. The standard treatment for locally advanced or metastatic UC is enfortumab vedotin (EV) given with pembrolizumab. The goals of this study are to learn about: * The safety of the study treatment when given with standard treatment and if people tolerate it * The number of people who have the cancer respond (cancer gets smaller or goes away) with the new study treatment when given with standard treatment.

Detailed Description

This is a substudy of the master protocol MK-3475-U04 (KEYMAKER-U04)

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has histologically documented urothelial carcinoma (UC) that is locally advanced and unresectable or metastatic * Must provide a newly obtained or archival tumor tissue sample (core or excisional biopsy) * Must not have received prior systemic therapy for locally advanced or metastatic UC * If infected with Human Immunodeficiency Virus (HIV), has well controlled HIV on antiretroviral therapy * If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load before randomization * If participant has a history of hepatitis C virus (HCV), has undetectable HCV viral load before randomization Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing * Has active keratitis or corneal ulcerations * Has active inflammatory bowel disease requiring immunosuppressive medication, or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention * Has a history of uncontrolled diabetes * Has pleural effusion, ascites, and/or pericardial effusion that are symptomatic or require repeated drainage * Has active autoimmune disease that has required systemic treatment in the past 2 years * Has known additional malignancy that is progressing or has required active treatment within the past 2 years * Has known active central nervous system metastases and/or carcinomatous meningitis * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease * Has an active infection requiring systemic therapy * If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has concurrent active HBV and HCV infection * Has a history of stem cell/solid organ transplant

Interventions

DRUG

MK-3120

DRUG

EV

BIOLOGICAL

Pembrolizumab

DRUG

Rescue Medication

Interested in This Trial?

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Conditions

Bladder Cancer

Locations

UCSF Medical Center at Mission Bay ( Site 5044)

San Francisco, California 94158

United States

University of Chicago Medical Center ( Site 5037)

Chicago, Illinois 60637

United States

Cleveland Clinic Taussig Cancer ( Site 5036)

Cleveland, Ohio 44195

United States

Huntsman Cancer Institute ( Site 5041)

Salt Lake City, Utah 84112-5550

United States

FALP ( Site 5151)

Santiago, Region M. de Santiago 7500921

Chile

CHU de Bordeaux Hop St ANDRE ( Site 5607)

Bordeaux, Gironde 33075

France

Rambam Health Care Campus ( Site 5501)

Haifa, 3109601

Israel

Rabin Medical Center ( Site 5504)

Petah Tikva, 4941492

Israel

Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI AVL) ( Site 5302)

Amsterdam, North Holland 1066 CX

Netherlands

Erasmus MC ( Site 5303)

Rotterdam, South Holland 3015 GD

Netherlands

Severance Hospital, Yonsei University Health System ( Site 5903)

Seoul, 03722

South Korea

Asan Medical Center ( Site 5901)

Seoul, 05505

South Korea

Samsung Medical Center ( Site 5902)

Seoul, 06351

South Korea

Hospital Universitari Vall de Hebron ( Site 5767)

Barcelona, 08035

Spain

Hospital Clinico San Carlos ( Site 5765)

Madrid, 28040

Spain

St Bartholomew s Hospital ( Site 5206)

London, London, City of EC1A 7BE

United Kingdom