Recruiting

Phase 1

Phase 2

Investigational Agents & PembrolizumabA 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)

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT05562830

Conditions

Urothelial Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Zilovertamab vedotin

Pembrolizumab

MK-3120

Study Details

Brief 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.

Conditions

Urothelial Carcinoma

Study ID

NCT05562830

Start date

Nov 16, 2022

Status verified date

May, 2026

Completion date

Feb 26, 2029

Anticipated

Primary completion date

Feb 26, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

48 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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).

Interventions

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.

Primary outcome measure

Percentage of Participants Who Experienced At Least One Adverse Event (AE) [ Time Frame: Up to approximately 5 years ]
Percentage of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 5 years ]
Arm A: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 2 years ]
Arm B: ORR as Assessed by Investigator [ Time Frame: Up to approximately 2 years ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839 Trialsites@msd.com

Locations

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

Recruiting

Orange, California, United States, 92868

Contacts

Study Coordinator

714-509-2371

University of California San Francisco ( Site 1044)

Recruiting

San Francisco, California, United States, 94158

Contacts

Study Coordinator

415-476-4616

University of Chicago Medical Center ( Site 1037)

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Study Coordinator

855-702-8222

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

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Study Coordinator

888-600-4822

Siteman Cancer Center ( Site 1038)

Recruiting

St Louis, Missouri, United States, 63108

Contacts

Study Coordinator

800-600-3606

Memorial Sloan Kettering Cancer Center ( Site 1031)

Recruiting

New York, New York, United States, 10065

Contacts

Study Coordinator

646-888-4770

Cleveland Clinic-Taussig Cancer Center ( Site 1036)

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Study Coordinator

216-445-7728

UPMC Hillman Cancer Center ( Site 1014)

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Study Coordinator

412-623-4759

Huntsman Cancer Institute ( Site 1041)

Recruiting

Salt Lake City, Utah, United States, 84112-5500

Contacts

Study Coordinator

801-585-0155

Princess Margaret Cancer Centre ( Site 1106)

Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contacts

Study Coordinator

4169464501 2662

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

May 27, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-05-27.