Phase 2 enfortumab vedotin Nectin-4 ADC (MMAE tubulin payload) plus pembrolizumab PD-1 antibody

University of Utah’s Phase 2 PRESERVE study tests whether systemic enfortumab vedotin (Padcev; Astellas Pharma + Pfizer)—a Nectin-4–targeted antibody–drug conjugate delivering MMAE, a microtubule inhibitor—combined with pembrolizumab (Keytruda; Merck), a PD-1 (CD279)–blocking monoclonal antibody, can produce a durable clinical response that allows bladder preservation. It is a single-arm, treatment-naïve localized MIBC program focused on T2–T3N0M0 urothelial carcinoma, aiming to avoid cystectomy and also avoid radiotherapy in responders. The scientific angle is bringing the high-activity EV+PD-1 backbone earlier and using response-adapted management to potentially spare organ removal rather than automatically proceeding to definitive local therapy. Current curative-intent treatment includes cystectomy-based perioperative systemic therapy, now including EV+pembrolizumab and, for cisplatin-eligible patients, gemcitabine/cisplatin + durvalumab, while selected patients may pursue bladder-preserving trimodality therapy. PRESERVE asks whether EV+pembrolizumab can support an additional bladder-sparing strategy without cystectomy or radiotherapy.