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)
- Conditions
- Urothelial Carcinoma
- Interventions
- Registration Number
- NCT05562830
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 40
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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Zilovertamab vedotin 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced At Least One Adverse Event (AE) 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.
Percentage of Participants Who Discontinued Study Treatment Due to an AE 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
Objective Response Rate (ORR) 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) 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.
Trial Locations
- Locations (18)
FALP-UIDO ( Site 1151)
🇨🇱Santiago, Region M. De Santiago, Chile
Rambam Health Care Campus-Oncology ( Site 1501)
🇮🇱Haifa, Israel
Cleveland Clinic-Taussig Cancer Center ( Site 1036)
🇺🇸Cleveland, Ohio, United States
Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
🇦🇺Brisbane, Queensland, Australia
Anschutz Cancer Pavilion ( Site 1017)
🇺🇸Aurora, Colorado, United States
UPMC Hillman Cancer Center ( Site 1014)
🇺🇸Pittsburgh, Pennsylvania, United States
Washington University ( Site 1038)
🇺🇸Saint Louis, Missouri, United States
Rabin Medical Center-Oncology ( Site 1504)
🇮🇱Petah Tikva, Israel
Rigshospitalet-Dept. of Oncology ( Site 1701)
🇩🇰Copenhagen, Hovedstaden, Denmark
Bradfordhill-Clinical Area ( Site 1155)
🇨🇱Santiago, Region M. De Santiago, Chile
Severance Hospital, Yonsei University Health System ( Site 1903)
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron ( Site 1767)
🇪🇸Barcelona, Spain
Asan Medical Center ( Site 1901)
🇰🇷Seoul, Korea, Republic of
Sheba Medical Center-ONCOLOGY ( Site 1503)
🇮🇱Ramat Gan, Israel
Samsung Medical Center ( Site 1902)
🇰🇷Seoul, Korea, Republic of
Hospital Clinico San Carlos ( Site 1765)
🇪🇸Madrid, Spain
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
🇺🇸Orange, California, United States
Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)
🇺🇸Indianapolis, Indiana, United States