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)

NCT07232602 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 3475-04DU1111-1322-37132025-522253-19-00MK-3475-04D
• Study Type: interventional
• Target: 55
• Locations: 8 countries
• Sites: 14

Brief 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.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experience an Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.

  Up to approximately 27 months

• Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

  DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next treatment. The number of participants who experience a DLT as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 will be presented.

  Up to approximately 21 days

• Number of Participants Who Discontinue Study Treatment Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinue study intervention due to an AE will be reported.

  Up to approximately 24 months

• Objective Response Rate (ORR) as Assessed by Investigator

  ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Investigator will be presented.

  Up to approximately 58 months

Secondary Outcomes (13)

• Duration of Response (DOR) as Assessed by Investigator

  Up to approximately 58 months

• Serum Maximum Concentration (Cmax) of MK-3120 Antibody-Drug Conjugate (ADC)

  Predose and at designated time points post-dose (up to approximately 24 months)

• Serum Trough Concentration (Ctrough) of MK-3120 ADC

  Predose and at designated time points post-dose (up to approximately 24 months)

• Serum Cmax of MK-3120 Total Antibodies (TAb)

  Predose and at designated time points post-dose (up to approximately 24 months)

• Serum Ctrough of MK-3120 TAb

  Predose and at designated time points post-dose (up to approximately 24 months)

Study Arms (1)

Arm A: MK-3120 + Enfortumab Vedotin (EV) + Pembrolizumab

EXPERIMENTAL

Participants will receive MK-3120 administered intravenously on Day 1 and Day 8 of each 3-week cycle and EV administered intravenously on Day 1 and Day 8 of each 3-week cycle until documented disease progression or any other discontinuation criterion is met and Pembrolizumab 200 mg administered intravenously on Day 1 of each 3-week cycle for up to 35 cycles (\~2 years).

Drug: MK-3120; Drug: EV; Biological: Pembrolizumab; Drug: Rescue Medication

Interventions

Pembrolizumab BIOLOGICAL

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

Also known as: MK-3475, KEYTRUDA®

Arm A: MK-3120 + Enfortumab Vedotin (EV) + Pembrolizumab

MK-3120 DRUG

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

Arm A: MK-3120 + Enfortumab Vedotin (EV) + Pembrolizumab

EV DRUG

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

Also known as: AGS 22M6E, AGS-22CE

Arm A: MK-3120 + Enfortumab Vedotin (EV) + Pembrolizumab

Rescue Medication DRUG

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

Arm A: MK-3120 + Enfortumab Vedotin (EV) + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (14)

UCSF Medical Center at Mission Bay ( Site 5044)

San Francisco, California, 94158, United States

RECRUITING

Cleveland Clinic Taussig Cancer ( Site 5036)

Cleveland, Ohio, 44195, United States

RECRUITING

Huntsman Cancer Institute ( Site 5041)

Salt Lake City, Utah, 84112-5550, United States

RECRUITING

FALP ( Site 5151)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

CHU de Bordeaux Hop St ANDRE ( Site 5607)

Bordeaux, Gironde, 33075, France

RECRUITING

Rambam Health Care Campus ( Site 5501)

Haifa, 3109601, Israel

RECRUITING

Rabin Medical Center ( Site 5504)

Petah Tikva, 4941492, Israel

RECRUITING

Erasmus MC ( Site 5303)

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 5903)

Seoul, 03722, South Korea

RECRUITING

Asan Medical Center ( Site 5901)

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center ( Site 5902)

Seoul, 06351, South Korea

RECRUITING

Hospital Universitari Vall de Hebron ( Site 5767)

Barcelona, 08035, Spain

RECRUITING

Hospital Clinico San Carlos ( Site 5765)

Madrid, 28040, Spain

RECRUITING

St Bartholomew s Hospital ( Site 5206)

London, London, City of, EC1A 7BE, United Kingdom

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

enfortumab vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 18, 2025
• Study Start: February 9, 2026
• Primary Completion (Estimated): July 8, 2031
• Study Completion (Estimated): July 8, 2031
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (1); KR (3); ES (2); NL (1); US (3); GB (1); CL (1); IL (2)