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)
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
Merck Sharp & Dohme LLC
48 participants
Nov 16, 2022
INTERVENTIONAL
Conditions
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.
Eligibility
Exclusion Criteria11
- Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.
- Arm A: 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.
- Arm A: 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.
- Arm B: PD-1/L1 refractory locally advanced or mUC as evidenced by: EITHER disease progression after treatment with an anti-PD-1/L1 mAb for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies; OR disease recurrence after treatment with an anti-PD-1/L1 mAb for MIUC administered as monotherapy or in combination with other checkpoint therapies >12 months after last dose of treatment with an anti-PD-1/L1 mAb.
- Arm B: Participants must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion from a metastatic site or from a primary tumor that has become locally advanced and not previously irradiated.
- 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.
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Interventions
Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles
Administered via IV infusion on Day 1 of each 6 week cycle.
Administered as an IV infusion on Day 1, Day 15, and Day 29 of each 6 week cycle.
Locations(28)
View Full Details on ClinicalTrials.gov
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NCT05562830