Enfortumab vedotin (Nectin-4 ADC) + pembrolizumab (PD-1) lifts EFS/OS vs cisplatin-gemcitabine in MIBC

Enfortumab vedotin is a Nectin-4–directed antibody–drug conjugate (MMAE payload) and pembrolizumab is a PD-1 inhibitor; in the Phase 3, open-label KEYNOTE-B15/EV-304 trial (NCT04700124), cisplatin-eligible muscle-invasive bladder cancer patients were randomized to perioperative EV+pembro (neoadjuvant 4 cycles → cystectomy → adjuvant EV 5 cycles + pembro 13 cycles) vs neoadjuvant cisplatin-gemcitabine (GC) x4 cycles → cystectomy (n=405 vs n=403; median follow-up 33.6 months; cystectomy performed in 86.7% vs 89.6%). At 2 years, event-free survival was 79.4% vs 66.2% (HR 0.53, 95% CI 0.41–0.70; P<0.001) and overall survival was 86.9% vs 81.3% (HR 0.65, 95% CI 0.48–0.89; P=0.006), with pathologic complete response 55.8% vs 32.5% (P<0.001)—notably above the ~30% pCR often cited for cisplatin-based neoadjuvant chemotherapy and in line with GC benchmarks typically in the ~20–36% range. Grade ≥3 AEs (any cause) were higher with EV+pembro (75.7% vs 67.2%), underscoring that the survival win comes with added toxicity burden relative to GC.