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 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
- Urothelial Carcinoma
At a glance
- Phase
- Phase 1
- Study type
- Interventional
- Sponsor
- Merck Sharp & Dohme LLC
- Enrolment target
- 48
- Started
- 16 November 2022
- Main results due
- 26 February 2029
- Study sites
- 28
- Registry updated
- 28 September 2026
Can you take part?
- Aged 18 years and over.
- Open to any sex.
- You need the condition being studied — healthy volunteers are not accepted.
These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.
Read the full eligibility criteria
Inclusion Criteria: 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. Exclusion Criteria: * 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.
What this study is about
In the sponsor’s own words, from the registry.
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.
Study sites(28)
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
Orange, California, United States
Recruiting
University of California San Francisco ( Site 1044)
San Francisco, California, United States
Recruiting
Anschutz Cancer Pavilion ( Site 1017)
Aurora, Colorado, United States
Completed
University of Chicago Medical Center ( Site 1037)
Chicago, Illinois, United States
Recruiting
Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)
Indianapolis, Indiana, United States
Recruiting
Siteman Cancer Center ( Site 1038)
St Louis, Missouri, United States
Active, not recruiting
Memorial Sloan Kettering Cancer Center ( Site 1031)
New York, New York, United States
Recruiting
Cleveland Clinic-Taussig Cancer Center ( Site 1036)
Cleveland, Ohio, United States
Recruiting
UPMC Hillman Cancer Center ( Site 1014)
Pittsburgh, Pennsylvania, United States
Recruiting
Huntsman Cancer Institute ( Site 1041)
Salt Lake City, Utah, United States
Recruiting
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Site 1952)
Brisbane, Queensland, Australia
Completed
Princess Margaret Cancer Centre ( Site 1106)
Toronto, Ontario, Canada
Recruiting
FALP-UIDO ( Site 1151)
Santiago, Region M. de Santiago, Chile
Recruiting
Bradford Hill ( Site 1155)
Santiago, Region M. de Santiago, Chile
Recruiting
Rigshospitalet-Dept. of Oncology ( Site 1701)
Copenhagen, Capital Region, Denmark
Recruiting
Rambam Health Care Campus-Oncology ( Site 1501)
Haifa, Israel
Recruiting
Rabin Medical Center-Oncology ( Site 1504)
Petah Tikva, Israel
Recruiting
Sheba Medical Center-ONCOLOGY ( Site 1503)
Ramat Gan, Israel
Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1408)
Milan, Lombardy, Italy
Recruiting
Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Sperimentazioni Cliniche ( Site 1406)
Naples, Italy
Recruiting
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 1302)
Amsterdam, North Holland, Netherlands
Recruiting
Severance Hospital, Yonsei University Health System ( Site 1903)
Seoul, South Korea
Recruiting
Asan Medical Center ( Site 1901)
Seoul, South Korea
Recruiting
Samsung Medical Center ( Site 1902)
Seoul, South Korea
Recruiting
Hospital Universitari Vall d'Hebron ( Site 1767)
Barcelona, Catalonia, Spain
Recruiting
Hospital Clinico San Carlos ( Site 1765)
Madrid, Spain
Recruiting
St Bartholomew's Hospital ( Site 1206)
London, London, City of, United Kingdom
Recruiting
ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1201)
London, London, City of, United Kingdom
Recruiting
Showing 28 of 28 sites. 25 of the 28 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.
Source: ClinicalTrials.gov record NCT05562830. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.
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