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Urothelial CarcinomaPhase 1/2NCT05562830

A Substudy of Investigational Agents in Programmed Cell Death-1/Ligand 1 (PD-1/L1) Refractory Locally Advanced or Metastatic Urothelial Carcinoma (mUC) (MK-3475-04A)

A Phase 1/2 study testing Zilovertamab vedotin, Pembrolizumab and MK-3120 in people with Urothelial Carcinoma, run by Merck Sharp & Dohme LLC at 28 sites in 11 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

This substudy is part of an umbrella platform study which is designed to evaluate investigational agents with or without pembrolizumab in participants with urothelial carcinoma who are in need of new treatment options. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
Zilovertamab vedotin, Pembrolizumab and MK-3120
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
28 sitesin 11 countries
Study dates
16 Nov 2022to 26 Feb 2029
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 and exclusion criteria include but are not limited to the following:
  • Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
  • Arm A: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 monoclonal antibody (mAb) for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies OR disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive urothelial carcinoma (MIUC) administered as monotherapy.
  • Arm A: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation.
  • Arm B: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression after treatment with an anti-PD-1/L1 mAb for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies; OR disease recurrence after treatment with an anti-PD-1/L1 mAb for MIUC administered as monotherapy or in combination with other checkpoint therapies >12 months after last dose of treatment with an anti-PD-1/L1 mAb.
  • Arm B: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion from a metastatic site or from a primary tumor that has become locally advanced and not previously irradiated.

Who cannot join

  • Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.
  • Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.
  • Active infection requiring systemic therapy.
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
  • Known history of human immunodeficiency virus (HIV).
  • Known history of hepatitis B or known hepatitis C virus infection.

Trial locations and contacts

28 sites in 11 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

28 sites in 11 countries

United States10 sites, 8 recruiting

  • Anschutz Cancer Pavilion ( Site 1017)

    Aurora, Colorado, 80045

    Completed

  • University of Chicago Medical Center ( Site 1037)

    Chicago, Illinois, 60637

    Study Coordinator, 855-702-8222

    Recruiting

  • Cleveland Clinic-Taussig Cancer Center ( Site 1036)

    Cleveland, Ohio, 44195

    Study Coordinator, 216-445-7728

    Recruiting

  • Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)

    Indianapolis, Indiana, 46202

    Study Coordinator, 888-600-4822

    Recruiting

  • Memorial Sloan Kettering Cancer Center ( Site 1031)

    New York, New York, 10065

    Study Coordinator, 646-888-4770

    Recruiting

  • University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)

    Orange, California, 92868

    Study Coordinator, 714-509-2371

    Recruiting

  • UPMC Hillman Cancer Center ( Site 1014)

    Pittsburgh, Pennsylvania, 15232

    Study Coordinator, 412-623-4759

    Recruiting

  • Huntsman Cancer Institute ( Site 1041)

    Salt Lake City, Utah, 84112-5500

    Study Coordinator, 801-585-0155

    Recruiting

  • University of California San Francisco ( Site 1044)

    San Francisco, California, 94158

    Study Coordinator, 415-476-4616

    Recruiting

  • Siteman Cancer Center ( Site 1038)

    St Louis, Missouri, 63108

    Active, not recruiting

Other trials in United States

Israel3 sites, 3 recruiting

  • Rambam Health Care Campus-Oncology ( Site 1501)

    Haifa, 3109601

    Study Coordinator, +972-4-7776234

    Recruiting

  • Rabin Medical Center-Oncology ( Site 1504)

    Petah Tikva, 4941492

    Study Coordinator, 972 393 78077

    Recruiting

  • Sheba Medical Center-ONCOLOGY ( Site 1503)

    Ramat Gan, 5265601

    Study Coordinator, 03-5304498

    Recruiting

Other trials in Israel

South Korea3 sites, 3 recruiting

  • Severance Hospital, Yonsei University Health System ( Site 1903)

    Seoul, 03722

    Study Coordinator, +82222288138

    Recruiting

  • Asan Medical Center ( Site 1901)

    Seoul, 05505

    Study Coordinator, +82230105977

    Recruiting

  • Samsung Medical Center ( Site 1902)

    Seoul, 06351

    Study Coordinator, +82234103459

    Recruiting

Other trials in South Korea

Chile2 sites, 2 recruiting

  • FALP-UIDO ( Site 1151)

    Santiago, Region M. de Santiago, 7500921

    Study Coordinator, 56224205098

    Recruiting

  • Bradford Hill ( Site 1155)

    Santiago, Region M. de Santiago, 8420383

    Study Coordinator, +56229490970

    Recruiting

Other trials in Chile

Italy2 sites, 2 recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1408)

    Milan, Lombardy, 20133

    Study Coordinator, +390223904449

    Recruiting

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Sperimentazioni Cliniche ( Site 1406)

    Naples, 80131

    Study Coordinator, 00393331891929

    Recruiting

Other trials in Italy

Spain2 sites, 2 recruiting

  • Hospital Universitari Vall d'Hebron ( Site 1767)

    Barcelona, Catalonia, 08035

    Study Coordinator, +34934894158

    Recruiting

  • Hospital Clinico San Carlos ( Site 1765)

    Madrid, 28040

    Study Coordinator, +34913303546

    Recruiting

Other trials in Spain

United Kingdom2 sites, 2 recruiting

  • St Bartholomew's Hospital ( Site 1206)

    London, London, City of, EC1A 7BE

    Study Coordinator, +44 0203 416 5000

    Recruiting

  • ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1201)

    London, London, City of, SW3 6JJ

    Study Coordinator, +44 20 7352 8171

    Recruiting

Other trials in United Kingdom

Australia1 site

  • Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Site 1952)

    Brisbane, Queensland, 4029

    Completed

Other trials in Australia

Canada1 site, 1 recruiting

  • Princess Margaret Cancer Centre ( Site 1106)

    Toronto, Ontario, M5G 2M9

    Study Coordinator, 4169464501 2662

    Recruiting

Other trials in Canada

Denmark1 site, 1 recruiting

  • Rigshospitalet-Dept. of Oncology ( Site 1701)

    Copenhagen, Capital Region, 2100

    Study Coordinator, 00 45 35 45 35 45

    Recruiting

Other trials in Denmark

Netherlands1 site, 1 recruiting

  • Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 1302)

    Amsterdam, North Holland, 1066 CX

    Study Coordinator, +31 20 512 9111

    Recruiting

Other trials in Netherlands

About this study

Official title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A

This substudy is part of an umbrella platform study which is designed to evaluate investigational agents with or without pembrolizumab in participants with urothelial carcinoma who are in need of new treatment options. Substudy 04A will enroll participants with locally advanced or mUC whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors. The protocol infrastructure will enable the rolling assignment of investigational treatments.

Being tested
Zilovertamab vedotin, Pembrolizumab, MK-3120
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

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

  • Zilovertamab vedotinBiological

    Also called MK-2140, VLS-101

    Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    Administered via IV infusion on Day 1 of each 6 week cycle.

  • MK-3120Biological

    Administered as an IV infusion on Day 1, Day 15, and Day 29 of each 6 week cycle.

Study groups in NCT05562830
Study groupRoleWhat they receive
Arm A: Zilovertamab vedotinExperimentalParticipants will receive zilovertamab vedotin 2mg/kg administered on Day 1 and Day 8 of each 3 week cycle (Q3W) until documented disease progression or any other discontinuation criterion is met.
Receives: Biological: Zilovertamab vedotin
Arm B: Pembrolizumab and MK-3120ExperimentalParticipants will receive MK-3120 up to 5mg/kg administered on Day 1, Day 15 and Day 29 of each 6 week cycle until documented disease progression or any other discontinuation criterion is met and 400mg pembrolizumab on Day 1 of each 6 week cycle for up to 17 cycles (up to ~2 years).
Receives: Biological: Pembrolizumab; Biological: MK-3120

What is being measured

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

  1. Percentage of Participants Who Experienced At Least One Adverse Event (AE)

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.

    Measured: Up to approximately 5 years

  2. Percentage of Participants Who Discontinued Study Treatment Due to an AE

    An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment

    Measured: Up to approximately 5 years

  3. Arm A: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)

    ORR is defined as the percentage of participants who achieve a 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 Blinded Independent Central Review (BICR) will be presented.

    Measured: Up to approximately 2 years

  4. Arm B: ORR as Assessed by Investigator

    ORR is defined as the percentage of participants who achieve a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

    Measured: Up to approximately 2 years

Secondary outcomes (2)

  1. Arm A: Duration of Response (DOR) as Assessed by BICR

    For participants who demonstrate confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, 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 Blinded Independent Central Review (BICR) will be presented.

    Measured: Up to approximately 2 years

  2. Arm B: DOR as Assessed by Investigator

    For participants who demonstrate confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, 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 the investigator will be presented.

    Measured: Up to approximately 2 years

Timeline

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

  1. First posted3 Oct 2022
  2. Study start16 Nov 2022
  3. Primary completion26 Feb 2029 (estimated)
  4. Study completion26 Feb 2029 (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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05562830
Sponsor's protocol ID
3475-04A
Other IDs
MK-3475-04A, 2023-506384-34-00, U1111-1293-7548, 2020-004544-28, 2023
Status last verified
Sep 2026
First submitted
28 Sep 2022
Last updated
28 Sep 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 Zilovertamab vedotin, Pembrolizumab and MK-3120 in people with Urothelial Carcinoma, run by Merck Sharp & Dohme LLC at 28 sites in 11 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 6 inclusion and 6 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 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Israel, South Korea, Chile, Italy and 6 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?

Percentage of Participants Who Experienced At Least One Adverse Event (AE) (time frame: Up to approximately 5 years). 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 NCT05562830.

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 28 Sep 2026.

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