RecruitingPhase 1Phase 2NCT07232602

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)

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

Sponsor

Merck Sharp & Dohme LLC

Enrollment

55 participants

Start Date

Feb 9, 2026

Study Type

INTERVENTIONAL

Conditions

Bladder Cancer

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria6

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 Criteria14

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

DRUGMK-3120

Administered via intravenous (IV) infusion on day 1 and day 8 of each 3-week cycle

DRUGEV

Administered via IV infusion on day 1 and day 8 of each 3-week cycle

BIOLOGICALPembrolizumab

Administered via IV infusion on day 1 of each 3-week cycle

DRUGRescue Medication

Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medication is Granulocyte Colony-Stimulating Factor (G-CSF).