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NCT05562830PHASE1, PHASE2Recruiting

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)

Merck Sharp & Dohme LLC

Start Date

11/16/2022

Completion Date

2/26/2029

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 Criteria

Age Range: 18 years to No maximum

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.

Interventions

BIOLOGICAL

Zilovertamab vedotin

BIOLOGICAL

Pembrolizumab

BIOLOGICAL

MK-3120

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Conditions

Urothelial Carcinoma

Locations

University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)

Orange, California 92868

United States

University of California San Francisco ( Site 1044)

San Francisco, California 94158

United States

Anschutz Cancer Pavilion ( Site 1017)

Aurora, Colorado 80045

United States

University of Chicago Medical Center ( Site 1037)

Chicago, Illinois 60637

United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)

Indianapolis, Indiana 46202

United States

Siteman Cancer Center ( Site 1038)

St Louis, Missouri 63108

United States

Memorial Sloan Kettering Cancer Center ( Site 1031)

New York, New York 10065

United States

Cleveland Clinic-Taussig Cancer Center ( Site 1036)

Cleveland, Ohio 44195

United States

UPMC Hillman Cancer Center ( Site 1014)

Pittsburgh, Pennsylvania 15232

United States

Huntsman Cancer Institute ( Site 1041)

Salt Lake City, Utah 84112-5500

United States

Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Site 1952)

Brisbane, Queensland 4029

Australia

Princess Margaret Cancer Centre ( Site 1106)

Toronto, Ontario M5G 2M9

Canada

FALP-UIDO ( Site 1151)

Santiago, Region M. de Santiago 7500921

Chile

Bradford Hill ( Site 1155)

Santiago, Region M. de Santiago 8420383

Chile

Rigshospitalet-Dept. of Oncology ( Site 1701)

Copenhagen, Capital Region 2100

Denmark

Rambam Health Care Campus-Oncology ( Site 1501)

Haifa, 3109601

Israel

Rabin Medical Center-Oncology ( Site 1504)

Petah Tikva, 4941492

Israel

Sheba Medical Center-ONCOLOGY ( Site 1503)

Ramat Gan, 5265601

Israel

Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 1408)

Milan, Lombardy 20133

Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale-S.C. Sperimentazioni Cliniche ( Site 1406)

Naples, 80131

Italy

Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 1302)

Amsterdam, North Holland 1066 CX

Netherlands

Severance Hospital, Yonsei University Health System ( Site 1903)

Seoul, 03722

South Korea

Asan Medical Center ( Site 1901)

Seoul, 05505

South Korea

Samsung Medical Center ( Site 1902)

Seoul, 06351

South Korea

Hospital Universitari Vall d'Hebron ( Site 1767)

Barcelona, Catalonia 08035

Spain

Hospital Clinico San Carlos ( Site 1765)

Madrid, 28040

Spain

St Bartholomew's Hospital ( Site 1206)

London, London, City of EC1A 7BE

United Kingdom

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1201)

London, London, City of SW3 6JJ

United Kingdom