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)

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Metastatic Urothelial Carcinoma, Urothelial Neoplasms

In brief

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.

Key facts

Study ID: NCT05845814
Run by: Merck Sharp & Dohme LLC
People needed: 390
Starts: 2023-06-23
Expected to finish: 2027-05-31
Last updated by the study team: 2025-09-10

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.

You may not qualify if…

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

Where it is running

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
Hospital Clinico San Carlos ( Site 3765) — Madrid, Spain
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

Full record on ClinicalTrials.gov

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