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)

NCT ID: NCT05562830

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-16

Study Completion Date

2028-06-20

Brief Summary

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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.

Detailed Description

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Conditions

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Urothelial Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Zilovertamab vedotin

Participants will receive zilovertamab vedotin 2mg/kg administered on Day 1 and Day 8 of each 3 week cycle (Q3W) until documented disease progression or any other discontinuation criterion is met.

Group Type EXPERIMENTAL

Zilovertamab vedotin

Intervention Type BIOLOGICAL

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

Arm B: Pembrolizumab and MK-3120

Participants will receive MK-3120 up to 5mg/kg administered on Day 1, Day 15 and Day 29 of each 6 week cycle until documented disease progression or any other discontinuation criterion is met and 400mg pembrolizumab on Day 1 of each 6 week cycle for up to 17 cycles (up to \~2 years).

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

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

MK-3120

Intervention Type BIOLOGICAL

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

Interventions

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Zilovertamab vedotin

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

Intervention Type BIOLOGICAL

Pembrolizumab

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

Intervention Type BIOLOGICAL

MK-3120

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

Intervention Type BIOLOGICAL

Other Intervention Names

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MK-2140 VLS-101 MK-3475 KEYTRUDA®

Eligibility Criteria

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Exclusion Criteria

* 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.


* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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

Orange, California, United States

Site Status

Anschutz Cancer Pavilion ( Site 1017)

Aurora, Colorado, United States

Site Status

University of Chicago Medical Center ( Site 1037)

Chicago, Illinois, United States

Site Status

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

Indianapolis, Indiana, United States

Site Status

Siteman Cancer Center ( Site 1038)

St Louis, Missouri, United States

Site Status

Cleveland Clinic-Taussig Cancer Center ( Site 1036)

Cleveland, Ohio, United States

Site Status

UPMC Hillman Cancer Center ( Site 1014)

Pittsburgh, Pennsylvania, United States

Site Status

Huntsman Cancer Institute ( Site 1041)

Salt Lake City, Utah, United States

Site Status

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

Brisbane, Queensland, Australia

Site Status

FALP-UIDO ( Site 1151)

Santiago, Region M. de Santiago, Chile

Site Status

Bradford Hill ( Site 1155)

Santiago, Region M. de Santiago, Chile

Site Status

Rigshospitalet-Dept. of Oncology ( Site 1701)

Copenhagen, Capital Region, Denmark

Site Status

Rambam Health Care Campus-Oncology ( Site 1501)

Haifa, , Israel

Site Status

Rabin Medical Center-Oncology ( Site 1504)

Petah Tikva, , Israel

Site Status

Sheba Medical Center-ONCOLOGY ( Site 1503)

Ramat Gan, , Israel

Site Status

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

Napoli, , Italy

Site Status

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

Amsterdam, North Holland, Netherlands

Site Status

Severance Hospital, Yonsei University Health System ( Site 1903)

Seoul, , South Korea

Site Status

Asan Medical Center ( Site 1901)

Seoul, , South Korea

Site Status

Samsung Medical Center ( Site 1902)

Seoul, , South Korea

Site Status

Hospital Universitari Vall d'Hebron ( Site 1767)

Barcelona, Catalonia, Spain

Site Status

Hospital Clinico San Carlos ( Site 1765)

Madrid, , Spain

Site Status

ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1201)

London, London, City of, United Kingdom

Site Status

Countries

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United States Australia Chile Denmark Israel Italy Netherlands South Korea Spain United Kingdom

Related Links

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Other Identifiers

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MK-3475-04A

Identifier Type: OTHER

Identifier Source: secondary_id

2023-506384-34-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1293-7548

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-004544-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3475-04A

Identifier Type: -

Identifier Source: org_study_id