Home › Trials › NCT07232602

Adding MK-3120 to enfortumab vedotin and pembrolizumab for advanced urothelial (bladder) cancer

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents in Combination With Enfortumab Vedotin Plus Pembrolizumab as First-Line Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma: KEYMAKER-U04-Substudy 04D

Phase1; Phase2 Interventional Merck Sharp & Dohme LLC · NCT07232602

This study tests whether adding the investigational drug MK-3120 to standard enfortumab vedotin plus pembrolizumab helps people with locally advanced or metastatic urothelial (bladder) cancer.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment55 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionsenfortumab, pembrolizumab
Locations14 sites (San Francisco, California and 13 other locations)
Trial IDNCT07232602 on ClinicalTrials.gov

What this trial studies

This substudy of the KEYMAKER-U04 master protocol gives MK-3120 together with the established combination of enfortumab vedotin and pembrolizumab to adults with locally advanced unresectable or metastatic urothelial carcinoma. Phase 1 focuses on safety, tolerability, and identifying a recommended dose, and phase 2 examines anti-tumor activity such as response rate. Eligible participants must provide a newly obtained or archival tumor tissue sample and must not have received prior systemic therapy for advanced disease. The trial is sponsored by Merck and is being run at multiple U.S. cancer centers.

Who should consider this trial

Good fit: Adults with histologically confirmed locally advanced unresectable or metastatic urothelial carcinoma who have not received prior systemic therapy for advanced disease and who can provide a tumor biopsy are the intended candidates.

Not a fit: Patients who have already had systemic therapy for metastatic UC or who have significant uncontrolled ocular surface disease (for example severe dry eye, Meibomian gland disease, or blepharitis) or uncontrolled viral infections are unlikely to qualify or benefit.

Why it matters

Potential benefit: If successful, the combination could increase tumor shrinkage rates and prolong disease control compared with the current standard regimen.

How similar studies have performed: Enfortumab vedotin plus pembrolizumab is an established effective regimen for advanced urothelial cancer, and combining novel agents with this backbone has shown promising signals in early-phase work, though MK-3120 itself is still investigational.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

San Francisco, California and 13 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Bladder Cancer
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.