Phase 3 EV-309 tests enfortumab vedotin Nectin-4 ADC + pembrolizumab PD-1 inhibitor

This Phase 3, open-label, randomized, multicenter study (EV-309) evaluates bladder-preserving enfortumab vedotin plus pembrolizumab versus concurrent chemoradiotherapy (cCRT) in adults with non-metastatic muscle-invasive bladder cancer (cT2–T4a N0 M0) who are ineligible for or choose not to undergo cystectomy and have had no prior systemic therapy. Enfortumab vedotin (Padcev; Astellas Pharma + Seagen/Pfizer) is a Nectin-4–directed antibody–drug conjugate delivering MMAE, a microtubule (tubulin) inhibitor, while pembrolizumab (Keytruda; Merck) blocks PD-1 to restore antitumor T-cell activity. The comparator arm reflects real-world bladder-sparing care: external beam radiation with concurrent radiosensitizing chemotherapy options such as cisplatin, 5-fluorouracil + mitomycin C, or gemcitabine. The key scientific/commercial angle is whether a systemic ADC + immunotherapy doublet can replace (or outperform) cCRT as a non-surgical definitive approach. Today’s care for patients avoiding cystectomy is trimodality therapy with maximal TURBT followed by cCRT plus close cystoscopic surveillance, with salvage cystectomy if needed.