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)
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
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.
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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:
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Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.
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Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.
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Active infection requiring systemic therapy.
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Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
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Known history of human immunodeficiency virus (HIV).
-
Known history of hepatitis B or known hepatitis C virus infection.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic-Taussig Cancer Center ( Site 1036) | Cleveland | Ohio | United States | 44195 |
| 2 | Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si | Brisbane | Queensland | Australia | 4029 |
| 3 | Bradfordhill-Clinical Area ( Site 1155) | Santiago | Region M. De Santiago | Chile | 8420383 |
| 4 | Rigshospitalet-Dept. of Oncology ( Site 1701) | Copenhagen | Hovedstaden | Denmark | 2100 |
| 5 | Rambam Health Care Campus-Oncology ( Site 1501) | Haifa | Israel | 3109601 | |
| 6 | Rabin Medical Center-Oncology ( Site 1504) | Petah Tikva | Israel | 4941492 | |
| 7 | Sheba Medical Center-ONCOLOGY ( Site 1503) | Ramat Gan | Israel | 5265601 | |
| 8 | Severance Hospital, Yonsei University Health System ( Site 1903) | Seoul | Korea, Republic of | 03722 | |
| 9 | Asan Medical Center ( Site 1901) | Seoul | Korea, Republic of | 05505 | |
| 10 | Samsung Medical Center ( Site 1902) | Seoul | Korea, Republic of | 06351 | |
| 11 | Hospital Universitari Vall d'Hebron ( Site 1767) | Barcelona | Spain | 08035 | |
| 12 | Hospital Clinico San Carlos ( Site 1765) | Madrid | Spain | 28040 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 3475-04A
- MK-3475-04A
- 2020-004544-28