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Bladder CancerPhase 1/2NCT07232602

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 study testing MK-3120, EV and Pembrolizumab in people with Bladder Cancer, run by Merck Sharp & Dohme LLC at 17 sites in 8 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Bladder Cancer
What is being tested?
MK-3120, EV and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
17 sitesin 8 countries
Study dates
9 Feb 2026to 8 Jul 2031
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

17 sites in 8 countries. Contact the study team or a site near you to ask about taking part.

Toll Free Number contact

1-888-577-8839

Trialsites@msd.com

17 sites in 8 countries

United States5 sites, 5 recruiting

  • University of Chicago Medical Center ( Site 5037)

    Chicago, Illinois, 60637

    Study Coordinator, 773-702-1000

    Recruiting

  • Cleveland Clinic Taussig Cancer ( Site 5036)

    Cleveland, Ohio, 44195

    Study Coordinator, 216-444-8311

    Recruiting

  • Memorial Sloan Kettering Cancer Center ( Site 5031)

    New York, New York, 10065

    Study Coordinator, 347-798-9213

    Recruiting

  • Huntsman Cancer Institute ( Site 5041)

    Salt Lake City, Utah, 84112-5550

    Study Coordinator, 801-585-0155

    Recruiting

  • UCSF Medical Center at Mission Bay ( Site 5044)

    San Francisco, California, 94158

    Study Coordinator, 415-699-7286

    Recruiting

Other trials in United States

South Korea3 sites, 3 recruiting

  • Severance Hospital, Yonsei University Health System ( Site 5903)

    Seoul, 03722

    Study Coordinator, +8215887757

    Recruiting

  • Asan Medical Center ( Site 5901)

    Seoul, 05505

    Study Coordinator, +8216887575

    Recruiting

  • Samsung Medical Center ( Site 5902)

    Seoul, 06351

    Study Coordinator, +8215993114

    Recruiting

Other trials in South Korea

Israel2 sites, 2 recruiting

  • Rambam Health Care Campus ( Site 5501)

    Haifa, 3109601

    Study Coordinator, +97247772688

    Recruiting

  • Rabin Medical Center ( Site 5504)

    Petah Tikva, 4941492

    Study Coordinator, +97239377377

    Recruiting

Other trials in Israel

Netherlands2 sites, 2 recruiting

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

    Amsterdam, North Holland, 1066 CX

    Study Coordinator, +31205129111

    Recruiting

  • Erasmus MC ( Site 5303)

    Rotterdam, South Holland, 3015 GD

    Study Coordinator, +31107040704

    Recruiting

Other trials in Netherlands

Spain2 sites, 2 recruiting

  • Hospital Universitari Vall de Hebron ( Site 5767)

    Barcelona, 08035

    Study Coordinator, +34932543450

    Recruiting

  • Hospital Clinico San Carlos ( Site 5765)

    Madrid, 28040

    Study Coordinator, +34913303546

    Recruiting

Other trials in Spain

Chile1 site, 1 recruiting

  • Fundación Arturo López Pérez ( Site 5151)

    Santiago, Region M. de Santiago, 7500921

    Study Coordinator, +56956075934

    Recruiting

Other trials in Chile

France1 site, 1 recruiting

  • CHU de Bordeaux Hop St ANDRE ( Site 5607)

    Bordeaux, Gironde, 33075

    Study Coordinator, +33556794708

    Recruiting

Other trials in France

United Kingdom1 site, 1 recruiting

  • St Bartholomew s Hospital ( Site 5206)

    London, London, City of, EC1A 7BE

    Study Coordinator, +442078228498

    Recruiting

Other trials in United Kingdom

About this study

Official title: 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

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.
Read the detailed description

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

Conditions
Bladder Cancer
Being tested
MK-3120, EV, Pembrolizumab, Rescue Medication
Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-3120Drug

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

  • EVDrug

    Also called AGS 22M6E, AGS-22CE

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

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

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

  • Rescue MedicationDrug

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

Study groups in NCT07232602
Study groupRoleWhat they receive
Arm A: MK-3120 + Enfortumab Vedotin (EV) + PembrolizumabExperimentalParticipants 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).
Receives: Drug: MK-3120; Drug: EV; Biological: Pembrolizumab; Drug: Rescue Medication

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to approximately 27 months

  2. 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.

    Measured: Up to approximately 21 days

  3. 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.

    Measured: Up to approximately 24 months

  4. 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.

    Measured: Up to approximately 58 months

Secondary outcomes (13)

  1. Duration of Response (DOR) as Assessed by Investigator

    For participants who demonstrate a confirmed CR (disappearance of all target lesions) or 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), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by investigator will be presented.

    Measured: Up to approximately 58 months

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

    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 ADC.

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

  3. Serum Trough Concentration (Ctrough) of MK-3120 ADC

    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-3120 ADC.

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

  4. Serum Cmax of MK-3120 Total Antibodies (TAb)

    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 TAb.

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

  5. Serum Ctrough of MK-3120 TAb

    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-3120 TAb.

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

  6. Plasma Cmax of MK-3120 Free Payload

    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 Free Payload.

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

  7. Plasma Ctrough of MK-3120 Free Payload

    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-3120 Free Payload.

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

  8. Serum Cmax of EV ADC

    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of EV ADC.

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

  9. Serum Ctrough of EV ADC

    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of EV ADC.

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

  10. Serum Cmax of EV TAb

    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of Enfortumab Vedotin (EV) TAb.

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

  11. Serum Ctrough of EV TAb

    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of EV TAb.

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

  12. Plasma Cmax of EV Free Payload

    Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of Enfortumab Vedotin (EV) Free Payload.

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

  13. Plasma Ctrough of EV Free Payload

    Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of EV Free Payload.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2025
  2. Study start9 Feb 2026
  3. Primary completion8 Jul 2031 (estimated)
  4. Study completion8 Jul 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
55 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07232602
Sponsor's protocol ID
3475-04D
Other IDs
U1111-1322-3713, 2025-522253-19-00, MK-3475-04D, 2025
Status last verified
Sep 2026
First submitted
14 Nov 2025
Last updated
2 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MK-3120, EV and Pembrolizumab in people with Bladder Cancer, run by Merck Sharp & Dohme LLC at 17 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States, South Korea, Israel, Netherlands, Spain and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Toll Free Number (1-888-577-8839, Trialsites@msd.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience an Adverse Event (AE) (time frame: Up to approximately 27 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07232602.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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