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)

June 30, 2023 updated by: Merck Sharp & Dohme LLC

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
  • Chile
    • Region M. De Santiago
      • Santiago, Region M. De Santiago, Chile, 6900941
        • FALP-UIDO ( Site 1151)
      • Santiago, Region M. De Santiago, Chile, 8420383
        • Bradfordhill-Clinical Area ( Site 1155)
  • Denmark
    • Hovedstaden
      • Copenhagen, Hovedstaden, Denmark, 2100
        • Rigshospitalet-Dept. of Oncology ( Site 1701)
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus-Oncology ( Site 1501)
      • Petah Tikva, Israel, 4941492
        • Rabin Medical Center-Oncology ( Site 1504)
      • Ramat Gan, Israel, 5265601
        • Sheba Medical Center-ONCOLOGY ( Site 1503)
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital, Yonsei University Health System ( Site 1903)
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center ( Site 1901)
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center ( Site 1902)
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron ( Site 1767)
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos ( Site 1765)
  • United States
    • California
      • Orange, California, United States, 92868
        • University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Anschutz Cancer Pavilion ( Site 1017)
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University ( Site 1038)
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic-Taussig Cancer Center ( Site 1036)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center ( Site 1014)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.
  • 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.

  • 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.

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Biological: Zilovertamab vedotin
Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles
Other Names:
  • MK-2140
  • VLS-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced At Least One Adverse Event (AE)
Time Frame: 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.
Up to approximately 5 years
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: 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
Up to approximately 5 years
Objective Response Rate (ORR)
Time Frame: 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.
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: Up to approximately 2 years
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.
Up to approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 16, 2022

Primary Completion (Estimated)

October 28, 2027

Study Completion (Estimated)

October 28, 2027

Study Registration Dates

First Submitted

September 28, 2022

First Submitted That Met QC Criteria

September 28, 2022

First Posted (Actual)

October 3, 2022

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 30, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-04A
  • MK-3475-04A (Other Identifier: Merck)
  • 2020-004544-28 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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