Phase 2 enfortumab vedotin Nectin-4 ADC + pembrolizumab PD-1 inhibitor for bladder preservation.

This open-label, single-arm Phase 2 EV-209 study tests whether continuing enfortumab vedotin plus pembrolizumab can enable durable response and bladder-intact survival (including bladder intact at 2 years) in resectable muscle-invasive bladder cancer (MIBC). Enfortumab vedotin (Padcev; Astellas Pharma + Pfizer) is a Nectin-4–directed antibody–drug conjugate that delivers the MMAE microtubule inhibitor payload to tumor cells, while pembrolizumab (Keytruda; Merck) blocks PD-1 (CD279) to restore anti-tumor T-cell activity. Eligible patients are adults with predominantly urothelial carcinoma (≥50%) and stage cT2–T4aN0M0 or T1–T4aN1M0 who are candidates for radical cystectomy, but the study’s goal is to treat and monitor with intent to preserve the bladder when response is maintained. Participants receive enfortumab vedotin on days 1 and 8 plus pembrolizumab on day 1 of each 21-day cycle, with treatment stopping if there is insufficient benefit by 9 cycles, progression, or intolerance. Today’s care for most fit MIBC patients is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy (or trimodality bladder-sparing chemoradiation in selected patients), and this trial explores a systemic immunotherapy/ADC approach as an alternative path to organ preservation in surgical candidates.