EV-103: Enfortumab vedotin (Nectin-4 ADC) + pembrolizumab (PD-1) sustains 41.5% 5-year survival in 1L cisplatin-ineligible la/mUC

Enfortumab vedotin is a Nectin-4–directed antibody–drug conjugate delivering MMAE, combined here with pembrolizumab (anti–PD-1) as first-line therapy in EV-103 dose escalation/cohort A (Phase Ib/II; NCT03288545) for cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (n=45; 84.4% visceral disease; 55.6% CrCl<60mL/min) with median follow-up 62.1 months. Confirmed ORR was 73.3% with median DOR 22.1 months; median PFS 12.7 months and median OS 26.1 months, with an estimated 5-year OS rate of 41.5% and no new safety signals reported. By historical benchmarks for this cisplatin-ineligible 1L setting, pembrolizumab monotherapy delivers ~29% ORR and mOS ~11.3 months in KEYNOTE-052, and atezolizumab monotherapy ~23.5% ORR and mOS ~16.3 months in IMvigor210 cohort 1—so the depth of response and long-tail survival here look materially higher, albeit from a small single-arm cohort (and later validated in Phase III EV-302, where EV+P improved mOS to 31.5 vs 16.1 months vs platinum+gemcitabine; HR 0.468).