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)

Recruiting now · Phase 1/Phase 2

Conditions studied: Urothelial Carcinoma

In brief

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.

Key facts

Study ID: NCT05562830
Run by: Merck Sharp & Dohme LLC
People needed: 48
Starts: 2022-11-16
Expected to finish: 2029-02-26
Last updated by the study team: 2026-05-27

Who can join

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

You may qualify if…

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.

You may not qualify if…

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.

Where it is running

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1201) — London, London, City of, United Kingdom (enrolling)
University of California San Francisco ( Site 1044) — San Francisco, California, United States (enrolling)
St Bartholomew's Hospital ( Site 1206) — London, London, City of, United Kingdom (enrolling)
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045) — Orange, California, United States (enrolling)
University of Chicago Medical Center ( Site 1037) — Chicago, Illinois, United States (enrolling)
Indiana University Melvin and Bren Simon Cancer Center ( Site 1011) — Indianapolis, Indiana, United States (enrolling)
Siteman Cancer Center ( Site 1038) — St Louis, Missouri, United States (enrolling)
Memorial Sloan Kettering Cancer Center ( Site 1031) — New York, New York, United States (enrolling)
Cleveland Clinic-Taussig Cancer Center ( Site 1036) — Cleveland, Ohio, United States (enrolling)
UPMC Hillman Cancer Center ( Site 1014) — Pittsburgh, Pennsylvania, United States (enrolling)
Huntsman Cancer Institute ( Site 1041) — Salt Lake City, Utah, United States (enrolling)
Princess Margaret Cancer Centre ( Site 1106) — Toronto, Ontario, Canada (enrolling)
FALP-UIDO ( Site 1151) — Santiago, Region M. de Santiago, Chile (enrolling)
Bradford Hill ( Site 1155) — Santiago, Region M. de Santiago, Chile (enrolling)
Rigshospitalet-Dept. of Oncology ( Site 1701) — Copenhagen, Capital Region, Denmark (enrolling)
Rambam Health Care Campus-Oncology ( Site 1501) — Haifa, Israel (enrolling)
Rabin Medical Center-Oncology ( Site 1504) — Petah Tikva, Israel (enrolling)
Sheba Medical Center-ONCOLOGY ( Site 1503) — Ramat Gan, Israel (enrolling)
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1408) — Milan, Lombardy, Italy (enrolling)
Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Sperimentazioni Cliniche ( Site 1406) — Naples, Italy (enrolling)
Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 1302) — Amsterdam, North Holland, Netherlands (enrolling)
Severance Hospital, Yonsei University Health System ( Site 1903) — Seoul, South Korea (enrolling)
Asan Medical Center ( Site 1901) — Seoul, South Korea (enrolling)
Samsung Medical Center ( Site 1902) — Seoul, South Korea (enrolling)
Hospital Universitari Vall d'Hebron ( Site 1767) — Barcelona, Catalonia, Spain (enrolling)

Full record on ClinicalTrials.gov

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