Landmark 304 Trial Shows PADCEV-Keytruda Combo Breakthrough in Bladder Cancer Treatment

Astellas Pharma and Pfizer have unveiled encouraging findings from their Phase 3 EV-304 study (KEYNOTE-B15), marking a significant shift in how muscle-invasive bladder cancer might be treated. The trial centered on combining PADCEV (enfortumab vedotin)—a Nectin-4 targeting antibody-drug conjugate—with Keytruda (pembrolizumab), a PD-1 inhibitor, and tested this pairing as both pre- and post-surgical therapy against conventional platinum-based chemotherapy.

Key Trial Outcomes and Clinical Significance

What makes the 304 results particularly noteworthy is that PADCEV plus Keytruda achieved improvements across multiple fronts. The combination succeeded in its primary goal by showing substantial gains in event-free survival (EFS) with statistical significance. Beyond that, it also crossed a critical secondary threshold with meaningful overall survival (OS) improvements—something rarely seen in this patient population when administered around surgical intervention.

The regimen’s performance in pathologic complete response (pCR) rates further strengthens the case: patients receiving the dual therapy showed clinically substantial improvements compared to those given standard neoadjuvant chemotherapy alone. Notably, this positions PADCEV plus Keytruda as the first platinum-free treatment option to deliver benefits in both event-free and overall survival metrics among cisplatin-eligible MIBC patients during the perioperative window.

Safety and Future Implications

The safety data remained consistent with established profiles for both agents, indicating the combination was well-tolerated throughout the trial. Combined with the parallel achievements from the EV-303 investigation, these 304 trial outcomes suggest PADCEV plus Keytruda could reshape the standard treatment landscape for early-stage bladder cancer by eliminating the need for platinum-based chemotherapy.

Researchers plan to present detailed 304 findings at forthcoming medical conferences while engaging regulatory bodies globally on potential approval pathways. This dual-pronged approach could accelerate the transition of this platinum-free regimen into routine clinical practice for eligible patients.