Astellas Pharma and Pfizer have announced that the FDA has accepted a supplemental Biologics License Application for Padcev (enfortumab vedotin) in combination with Keytruda (pembrolizumab) for priority review. The application seeks approval for the combination as a perioperative treatment—administered both before and after surgery—for patients with muscle invasive bladder cancer (MIBC), regardless of their eligibility for cisplatin chemotherapy. The FDA has set a target action date of August 17, 2026.

Clinical evidence from the EV 304 trial

The submission is based on data from the Phase 3 EV 304 trial, which compared the combination against the standard neoadjuvant chemotherapy of gemcitabine and cisplatin. Results presented at the 2026 ASCO Genitourinary Cancers Symposium showed a 47% reduction in the risk of tumor recurrence, progression, or death. Furthermore, the risk of death was reduced by 35% compared to the standard of care. The combination also achieved a pathological complete response rate of 55.8% at the time of surgery, nearly double the 32.5% seen in the chemotherapy arm.

Potential for a new standard of care

While the regimen was approved in late 2025 for patients ineligible for cisplatin, this new filing aims to expand that access to all MIBC patients. If approved, it would become the first and only perioperative treatment for MIBC that does not depend on cisplatin eligibility. Currently, many patients face a recurrence rate of over 50% even after successful surgery, highlighting the clinical necessity for more effective systemic therapies.

Leadership commentary

Moitreyee Chatterjee Kishore, Ph.D., head of oncology development at Astellas, emphasized the importance of these findings:

“The data from the EV-304 trial take us another step closer to bringing perioperative enfortumab vedotin plus pembrolizumab to patients with muscle-invasive bladder cancer regardless of cisplatin eligibility, who still face a recurrence rate of more than fifty percent despite curative-intent surgery, highlighting the ongoing need for improved treatment strategies.”

Jeff Legos, Ph.D., chief oncology officer at Pfizer, discussed the impact on the patient experience:

“For people with muscle‑invasive bladder cancer, surgery is often just the beginning of a long and uncertain journey, with far too many patients seeing their cancer return. If approved, perioperative PADCEV plus pembrolizumab could meaningfully change that experience, potentially helping patients reduce the risk of recurrence and live longer, regardless of whether they are eligible for cisplatin.”

Safety and next steps

The safety profile observed during the EV 304 trial remained consistent with previous studies of the combination, with no new safety signals identified. Astellas and Pfizer intend to engage with global health authorities to discuss these results for potential regulatory filings in other markets. For now, the focus remains on the upcoming August PDUFA date, which could redefine the treatment landscape for bladder cancer in the United States.