A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04)
NCT ID: NCT05845814
Last Updated: 2025-09-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
390 participants
INTERVENTIONAL
2023-06-23
2027-05-31
Brief Summary
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Detailed Description
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With Amendment 2, participants will discontinue treatment with coformulated vibostolimab/pembrolizumab (Arm B) and be transitioned to pembrolizumab only. Per protocol, no analysis of Part 2 primary or secondary outcome measures (including efficacy or safety) will occur since Part 2 of the study will no longer take place.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: Coformulated favezelimab/pembrolizumab plus EV
Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) as an intravenous (IV) infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.
Coformulated favezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion
EV
1.25 mg/kg IV infusion
Arm B: Coformulated vibostolimab/pembrolizumab plus EV
Participants will receive coformulated vibostolimab/pembrolizumab (200 mg/200 mg) as an IV infusion on Day 1 of every 3-week cycle, for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision.
Coformulated vibostolimab/pembrolizumab
Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion
EV
1.25 mg/kg IV infusion
Arm C: Pembrolizumab plus EV
Participants will receive 200 mg pembrolizumab as an IV infusion on Day 1 of every 3-week cycle for up to \~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle, until disease progression, intolerable toxicity, or investigator decision.
EV
1.25 mg/kg IV infusion
Pembrolizumab
200 mg IV infusion
Interventions
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Coformulated favezelimab/pembrolizumab
Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion
Coformulated vibostolimab/pembrolizumab
Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion
EV
1.25 mg/kg IV infusion
Pembrolizumab
200 mg IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Participants with mixed histology are eligible provided the urothelial component is ≥50% (and \<10% plasmacytoid component)
* Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally)
* Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted:
* Participants that received neoadjuvant or adjuvant chemotherapy are permitted.
* Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence \>12 months from completion of therapy are permitted.
* 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. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.
* Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement or with \<Grade 2 neuropathy are eligible.
Exclusion Criteria
* Central nervous system (CNS) metastases are permitted on-study if all of the following are true: a) CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis; b) the participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment); c) participant does not have leptomeningeal disease.
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
* Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
* Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
* Has a history of uncontrolled diabetes.
* Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection (viral, bacterial, or fungal) requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Has hepatitis B or hepatitis C virus infection.
* Has had major surgery within 4 weeks prior to first dose of study intervention.
* Has had an allogenic tissue/solid organ transplant
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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Moores Cancer Center ( Site 3028)
La Jolla, California, United States
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 3045)
Orange, California, United States
UCSF Medical Center at Mission Bay ( Site 3044)
San Francisco, California, United States
Anschutz Cancer Pavilion ( Site 3017)
Aurora, Colorado, United States
Emory University School of Medicine ( Site 3043)
Atlanta, Georgia, United States
Indiana University Melvin and Bren Simon Cancer Center ( Site 3011)
Indianapolis, Indiana, United States
Dana-Farber Cancer Institute ( Site 3047)
Boston, Massachusetts, United States
Siteman Cancer Center ( Site 3038)
St Louis, Missouri, United States
Icahn School of Medicine at Mount Sinai ( Site 3018)
New York, New York, United States
Memorial Sloan Kettering Cancer Center ( Site 3031)
New York, New York, United States
Duke Cancer Institute ( Site 3027)
Durham, North Carolina, United States
Cleveland Clinic-Taussig Cancer Center ( Site 3036)
Cleveland, Ohio, United States
UPMC Hillman Cancer Center ( Site 3014)
Pittsburgh, Pennsylvania, United States
Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 3041)
Salt Lake City, Utah, United States
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Site 3951)
Brisbane, Queensland, Australia
Austin Health-Cancer Clinical Trials Centre ( Site 3950)
Heidelberg, Victoria, Australia
The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 3105)
Ottawa, Ontario, Canada
Sunnybrook Research Institute - Odette Cancer Centre ( Site 3108)
Toronto, Ontario, Canada
Princess Margaret Cancer Centre ( Site 3106)
Toronto, Ontario, Canada
FALP-UIDO ( Site 3151)
Santiago, Region M. de Santiago, Chile
Bradfordhill-Clinical Area ( Site 3155)
Santiago, Region M. de Santiago, Chile
ONCOCENTRO APYS-ACEREY ( Site 3158)
Viña del Mar, Región de Valparaíso, Chile
Bradford Hill Norte ( Site 3152)
Antofagasta, , Chile
CHU de Bordeaux Hop St ANDRE ( Site 3607)
Bordeaux, Aquitaine, France
Centre Georges François Leclerc-Centre de recherche clinique ( Site 3608)
Dijon, Cote-d Or, France
Oncopole Claudius Regaud ( Site 3610)
Toulouse, Haute-Garonne, France
centre hospitalier lyon sud ( Site 3606)
Pierre-Bénite, Rhone, France
Hôpital Européen Georges Pompidou ( Site 3605)
Paris, , France
Rambam Health Care Campus-Oncology Division ( Site 3501)
Haifa, , Israel
Rabin Medical Center-Oncology ( Site 3504)
Petah Tikva, , Israel
Sheba Medical Center-ONCOLOGY ( Site 3503)
Ramat Gan, , Israel
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 3406)
Napoli, Campania, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3405)
Milan, Lombardy, Italy
Ospedale San Raffaele-Oncologia Medica ( Site 3403)
Milan, , Italy
Maastricht UMC+ ( Site 3304)
Maastricht, Limburg, Netherlands
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 3302)
Amsterdam, North Holland, Netherlands
Erasmus Medisch Centrum-Medical Oncology ( Site 3303)
Rotterdam, South Holland, Netherlands
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 3903)
Seoul, , South Korea
Asan Medical Center-Department of Oncology ( Site 3901)
Seoul, , South Korea
Samsung Medical Center ( Site 3902)
Seoul, , South Korea
Hospital Universitari Vall d'Hebron ( Site 3767)
Barcelona, Catalonia, Spain
Hospital Clinico San Carlos ( Site 3765)
Madrid, , Spain
Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 3802)
Kaohsiung City, , Taiwan
National Cheng Kung University Hospital-Clinical Trial Center ( Site 3803)
Tainan City, , Taiwan
National Taiwan University Hospital-Oncology ( Site 3801)
Taipei, , Taiwan
St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 3206)
London, London, City of, United Kingdom
ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 3201)
London, London, City of, United Kingdom
Countries
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Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-04B
Identifier Type: OTHER
Identifier Source: secondary_id
2023-506385-30-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1293-7564
Identifier Type: REGISTRY
Identifier Source: secondary_id
2022-001371-14
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
3475-04B
Identifier Type: -
Identifier Source: org_study_id
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