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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)

Primary Purpose

Urothelial Carcinoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Zilovertamab vedotin
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Urothelial Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
  • Anschutz Cancer Pavilion ( Site 1017)
  • Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)
  • Washington University ( Site 1038)
  • Cleveland Clinic-Taussig Cancer Center ( Site 1036)
  • UPMC Hillman Cancer Center ( Site 1014)
  • Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
  • FALP-UIDO ( Site 1151)
  • Bradfordhill-Clinical Area ( Site 1155)
  • Rigshospitalet-Dept. of Oncology ( Site 1701)
  • Rambam Health Care Campus-Oncology ( Site 1501)
  • Rabin Medical Center-Oncology ( Site 1504)
  • Sheba Medical Center-ONCOLOGY ( Site 1503)
  • Severance Hospital, Yonsei University Health System ( Site 1903)
  • Asan Medical Center ( Site 1901)
  • Samsung Medical Center ( Site 1902)
  • Hospital Universitari Vall d'Hebron ( Site 1767)
  • Hospital Clinico San Carlos ( Site 1765)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zilovertamab vedotin

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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
Objective Response Rate (ORR)
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.

Secondary Outcome Measures

Duration of Response (DOR)
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.

Full Information

First Posted
September 28, 2022
Last Updated
June 30, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05562830
Brief Title
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)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 16, 2022 (Actual)
Primary Completion Date
October 28, 2027 (Anticipated)
Study Completion Date
October 28, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urothelial Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zilovertamab vedotin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Zilovertamab vedotin
Other Intervention Name(s)
MK-2140, VLS-101
Intervention Description
Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experienced At Least One Adverse Event (AE)
Description
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
Title
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Description
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
Title
Objective Response Rate (ORR)
Description
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
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Anschutz Cancer Pavilion ( Site 1017)
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Washington University ( Site 1038)
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cleveland Clinic-Taussig Cancer Center ( Site 1036)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
UPMC Hillman Cancer Center ( Site 1014)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
FALP-UIDO ( Site 1151)
City
Santiago
State/Province
Region M. De Santiago
ZIP/Postal Code
6900941
Country
Chile
Facility Name
Bradfordhill-Clinical Area ( Site 1155)
City
Santiago
State/Province
Region M. De Santiago
ZIP/Postal Code
8420383
Country
Chile
Facility Name
Rigshospitalet-Dept. of Oncology ( Site 1701)
City
Copenhagen
State/Province
Hovedstaden
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Rambam Health Care Campus-Oncology ( Site 1501)
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Rabin Medical Center-Oncology ( Site 1504)
City
Petah Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Sheba Medical Center-ONCOLOGY ( Site 1503)
City
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Severance Hospital, Yonsei University Health System ( Site 1903)
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center ( Site 1901)
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center ( Site 1902)
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Hospital Universitari Vall d'Hebron ( Site 1767)
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinico San Carlos ( Site 1765)
City
Madrid
ZIP/Postal Code
28040
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information

Learn more about this trial

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)

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