A Phase 1/2 interventional study of Zilovertamab vedotin and Pembrolizumab in Urothelial Carcinoma, sponsored by Merck Sharp & Dohme LLC. Recruiting at 28 sites in 11 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Merck Sharp & Dohme LLC · Phase 1/2, Interventional, and Treatment
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.
The main inclusion and exclusion criteria include but are not limited to the following:
Exclusion Criteria:
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.
Biological: Zilovertamab vedotin
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).
Biological: Pembrolizumab · Biological: MK-3120
Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles
Also known as: MK-2140, VLS-101
Administered via IV infusion on Day 1 of each 6 week cycle.
Also known as: MK-3475, KEYTRUDA®
Administered as an IV infusion on Day 1, Day 15, and Day 29 of each 6 week cycle.
Percentage of Participants Who Experienced At Least One Adverse Event (AE)
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.
Time frame: Up to approximately 5 years
Percentage of Participants Who Discontinued Study Treatment Due to an AE
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
Time frame: Up to approximately 5 years
Arm A: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
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.
Time frame: Up to approximately 2 years
Arm B: ORR as Assessed by Investigator
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.
Time frame: Up to approximately 2 years
Arm A: Duration of Response (DOR) as Assessed by BICR
For participants who demonstrate confirmed 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, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time frame: Up to approximately 2 years
Arm B: DOR as Assessed by Investigator
For participants who demonstrate confirmed 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, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by the investigator will be presented.
Time frame: Up to approximately 2 years
Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Merck Sharp & Dohme LLC