This is a single-arm, open-label, non-randomized Phase II trial evaluating the efficacy of induction therapy with enfortumab vedotin (EV) plus pembrolizumab (P) for 18 weeks (6 cycles), followed by maintenance pembrolizumab in treatment-naïve patients with metastatic urothelial carcinoma (mUC). Approximately 97 patients will be enrolled. Induction consists of EV (1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle; starting dose of 1 mg/kg allowed) and P (200 mg IV on Day 1 of each cycle). Radiographic assessments occur after 3 and 6 cycles. Patients achieving complete or partial response transition to maintenance P (400 mg IV every 6 weeks or 200 mg IV every 3 weeks) for up to 2 years. Dose modifications for EV are permitted per protocol; no dose adjustments for P. Treatment continues until disease progression, unacceptable toxicity, or completion of maintenance therapy. Patients will enter long-term or survival follow-up as applicable.
Patients must have histologically and radiographically confirmed locally advanced, unresectable urothelial carcinoma.
Patients should not have received prior systemic therapy for metastatic disease.
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
Patients may have received prior neoadjuvant or adjuvant immune checkpoint inhibitor therapy for localized disease and are eligible if they completed the treatment ≥12 months prior to initiating treatment on this clinical trial.
Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer.
Grade 2 or higher baseline sensory or motor neuropathy.
Uncontrolled diabetes (HbA1c >8%)
Patients with uncontrolled and untreated central nervous system (CNS) metastases.
Fox Chase Cancer Center
Lead sponsor
United States Department of Defense
Collaborator