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)

NCT05562830 · tracked via the Priya Life Science UK tracker

Sponsor

Merck Sharp & Dohme LLC

Phase

Phase 1/2

Started

2022-11-16

Last updated

2026-05-27

Condition(s) studied

Urothelial Carcinoma

Investigational drug(s) / intervention(s)

Zilovertamab vedotinPembrolizumabMK-3120

Zilovertamab vedotin: Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles

Pembrolizumab: Administered via IV infusion on Day 1 of each 6 week cycle.

MK-3120: Administered as an IV infusion on Day 1, Day 15, and Day 29 of each 6 week cycle.

Study summary

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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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.

Primary outcome measure(s)

Percentage of Participants Who Experienced At Least One Adverse Event (AE) — Up to approximately 5 years
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Percentage of Participants Who Discontinued Study Treatment Due to an AE — Up to approximately 5 years
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment
Arm A: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) — Up to approximately 2 years
ORR is defined as the percentage of participants who achieve a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Arm B: ORR as Assessed by Investigator — Up to approximately 2 years
ORR is defined as the percentage of participants who achieve a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

Trial sites (28)

Facility	City	Region	Status
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)	Orange	California	Recruiting
University of California San Francisco ( Site 1044)	San Francisco	California	Recruiting
Anschutz Cancer Pavilion ( Site 1017)	Aurora	Colorado	Completed
University of Chicago Medical Center ( Site 1037)	Chicago	Illinois	Recruiting
Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)	Indianapolis	Indiana	Recruiting
Siteman Cancer Center ( Site 1038)	St Louis	Missouri	Recruiting
Memorial Sloan Kettering Cancer Center ( Site 1031)	New York	New York	Recruiting
Cleveland Clinic-Taussig Cancer Center ( Site 1036)	Cleveland	Ohio	Recruiting
UPMC Hillman Cancer Center ( Site 1014)	Pittsburgh	Pennsylvania	Recruiting
Huntsman Cancer Institute ( Site 1041)	Salt Lake City	Utah	Recruiting
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Site 1952)	Brisbane	Queensland	Completed
Princess Margaret Cancer Centre ( Site 1106)	Toronto	Ontario	Recruiting
FALP-UIDO ( Site 1151)	Santiago	Region M. de Santiago	Recruiting
Bradford Hill ( Site 1155)	Santiago	Region M. de Santiago	Recruiting
Rigshospitalet-Dept. of Oncology ( Site 1701)	Copenhagen	Capital Region	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	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	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	Recruiting
Hospital Clinico San Carlos ( Site 1765)	Madrid	Spain	Recruiting
St Bartholomew's Hospital ( Site 1206)	London	London, City of	Recruiting
ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1201)	London	London, City of	Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05562830 on ClinicalTrials.gov ↗ ← All trials in the UK