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ACTIVE NOT RECRUITING

NCT05845814

PHASE1/PHASE2

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)

Sponsor: Merck Sharp & Dohme LLC

View on ClinicalTrials.gov

Summary

This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and safety of coformulated favezelimab/pembrolizumab plus EV and coformulated vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of the treatment arms under study.

Official title: A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

390

Start Date

2023-06-23

Completion Date

2027-05-31

Last Updated

2025-09-10

Healthy Volunteers

Conditions

Metastatic Urothelial Carcinoma Urothelial Neoplasms

Interventions

BIOLOGICAL

Coformulated favezelimab/pembrolizumab

Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion

BIOLOGICAL

Coformulated vibostolimab/pembrolizumab

Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion

COMBINATION_PRODUCT

1.25 mg/kg IV infusion

BIOLOGICAL

Pembrolizumab

200 mg IV infusion

Inclusion Criteria: * Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC). * 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: * Has a known additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. * 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

Locations (47)

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)

Naples, 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, 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

Clinical Research Directory

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)

Summary

Key Details

Conditions

Interventions

Eligibility Criteria

Locations (47)