Breakthrough in Bladder Cancer Treatment: Astellas and Pfizer's Phase 3 EV-304 Trial Delivers Unprecedented Results

Astellas Pharma Inc. and Pfizer Inc. have announced a major advancement in cancer care, with positive Phase 3 EV-304 clinical trial data (also known as KEYNOTE-B15) demonstrating significant therapeutic potential in muscle-invasive bladder cancer (MIBC). The trial evaluated a novel combination approach using PADCEV (enfortumab vedotin), a Nectin-4 directed antibody-drug conjugate, paired with Keytruda® (pembrolizumab), a PD-1 inhibitor.

Redefining Treatment Standards Around Surgery

What makes this Phase 3 EV-304 achievement particularly notable is its evaluation of the combination in both neoadjuvant (pre-operative) and adjuvant (post-operative) settings—a comprehensive approach compared against the traditional standard of cisplatin-based chemotherapy. This dual-phase assessment provides clearer evidence for clinical decision-making across the entire surgical treatment window.

Primary and Secondary Endpoint Success

The trial successfully achieved its primary objective by demonstrating clinically meaningful and statistically significant improvements in event-free survival (EFS). Beyond this, the combination attained a critical secondary endpoint, showing significant enhancement in overall survival (OS)—a result that underscores genuine clinical benefit rather than mere intermediate markers.

A particularly important finding emerged in pathologic complete response (pCR) rates, where patients receiving PADCEV plus Keytruda showed clinically meaningful and statistically significant advantages compared to those receiving standard neoadjuvant chemotherapy alone. This metric suggests improved tumor control at the pathological level.

The Platinum-Free Advantage

Perhaps most significantly, the Phase 3 EV-304 results establish PADCEV combined with Keytruda as the first and only platinum-free regimen to simultaneously improve both event-free and overall survival in cisplatin-eligible patients with MIBC when administered perioperatively. This eliminates the necessity for traditional cisplatin-based approaches while maintaining superior efficacy—a meaningful shift in treatment philosophy for this patient population.

Safety and Regulatory Path Forward

The safety profile of this combination remained consistent with previously documented characteristics, indicating a manageable tolerability profile. Combined with positive findings from the preceding EV-303 trial, these Phase 3 EV-304 results position PADCEV plus Keytruda as a potential new platinum-free standard of care for earlier-stage bladder cancer management.

The trial findings will be presented at upcoming medical conferences and shared with global regulatory authorities to support future approval applications, potentially reshaping clinical practice in bladder cancer treatment.