NCT07221942

Pembrolizumab Maintenance After Enfortumab Vedotin (EV)/Pembro Induction in Front-Line Metastatic Urothelial Carcinoma

Pembrolizumab Maintenance After Enfortumab Vedotin/Pembrolizumab Induction in Front-Line Metastatic Urothelial Carcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 97 (estimated)
• Sponsor: Fox Chase Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This is a single-arm, open-label, non-randomized Phase II trial designed to evaluate 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, with recruitment anticipated to begin in 2025. Induction Phase (18 weeks): Patients will receive EV (1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle; starting dose of 1 mg/kg allowed per physician discretion) and P (200 mg IV on Day 1 of each cycle). The first radiographic assessment will occur after 3 cycles (approximately 9 weeks). Patients demonstrating clinical benefit (CR or PR per RECIST v1.1) will receive 3 additional cycles of EV/P, followed by a second radiographic assessment after 6 cycles (approximately 18 weeks). Patients achieving CR or PR will transition to the maintenance phase. Patients with stable disease may continue EV/P or transition to maintenance P based on patient/physician discretion. Patients experiencing progression during induction may seek alternative treatments. Maintenance Phase: Responding patients (CR/PR) will receive P at 400 mg IV every 6 weeks for up to 2 years, or 200 mg IV every 3 weeks per physician preference. The 2-year duration aligns with the maximum pembrolizumab exposure in EV-302. Radiographic assessments will occur every 12 weeks during maintenance. Patients will continue treatment until disease progression, unacceptable toxicity, or completion of maintenance therapy. Patients progressing on P maintenance may resume EV. Follow-Up: Patients will enter Survival Follow-up upon progression or toxicity requiring cessation of therapy. If a patient discontinues one drug due to toxicity or near complete response, they may continue on the other drug and remain on study. Both drugs may be discontinued early for toxicity or near complete response at physician discretion; these patients enter Long-term Follow-up. Patients who resume therapy after early discontinuation remain in Long-term Follow-up until progression, then transition to Survival Follow-up. Patients with suboptimal disease control or progression after EV schedule de-escalation may return to the original EV schedule at the highest tolerated dose per physician discretion. Dose adjustments for EV (1.25 mg/kg → 1 mg/kg → 0.75 mg/kg) are permitted per EV-302 guidelines. No dose adjustments for P will be made. Treatment may be held for up to 8 weeks for toxicity management; if held beyond 8 weeks, patients enter Long-term Follow-up.

Conditions

• Metastatic Urothelial Carcinoma
• Unresectable Urothelial Carcinoma
• Advanced Urothelial Carcinoma

Interventions

Type	Name	Description
DRUG	Enfortumab vedotin	EV will be administered at 1.25 mg/kg IV on Days 1 and 8 of each 21-day cycle
DRUG	Pembrolizumab	Pembrolizumab will be administered at 200 mg IV on Day 1 of each 21-day cycle

Timeline

• Start date: 2026-01-23
• Primary completion: 2028-09-01
• Completion: 2029-09-03
• First posted: 2025-10-29
• Last updated: 2026-02-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study