Astellas And Pfizer Report Positive Perioperative Data In PADCEV Plus Keytruda Improves Survival In Phase III EV-304 Trial In Muscle-Invasive Bladder Cancer

Astellas Pharma and Pfizer have reported positive topline results from an interim analysis of the Phase III EV-304 (KEYNOTE-B15) trial evaluating PADCEV™ (enfortumab vedotin) in combination with Keytruda® (pembrolizumab) as perioperative therapy in patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in event-free survival compared with standard neoadjuvant chemotherapy using gemcitabine and cisplatin. A key secondary endpoint of overall survival was also met.

Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, an EV-304 Principal Investigator, said “Despite available treatment options, nearly half of patients with muscle-invasive bladder cancer progress to metastatic disease within three years of diagnosis. The EV-304 results represent a key milestone in the new era of urothelial cancer treatment. Together, the EV-303 and EV-304 results show that perioperative enfortumab vedotin plus pembrolizumab can positively impact the treatment journey for patients with muscle-invasive bladder cancer, offering significant survival gains across cisplatin-ineligible and cisplatin-eligible patients, signaling a shift from conventional platinum-based chemotherapy and the potential to transform the standard of care.”

EV-304 is assessing PADCEV plus pembrolizumab as neoadjuvant treatment prior to surgery and as adjuvant therapy following surgery versus standard of care chemotherapy. In addition to improvements in EFS and OS, the combination achieved a statistically significant and clinically meaningful improvement in the pathologic complete response rate when used in the neoadjuvant setting. The safety profile of PADCEV plus pembrolizumab was consistent with the established safety profile of the regimen, with no new safety signals identified.

Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas, commented, “Building on the recent U.S. approval for cisplatin-ineligible patients living with MIBC, these positive EV-304 findings reinforce the potential of PADCEV plus pembrolizumab to improve survival outcomes for a broad population of patients living with muscle-invasive bladder cancer. Together with the EV-303 data, these results strengthen the evidence supporting this combination regimen as a treatment option for patients regardless of cisplatin eligibility. We are committed to bringing forth much-needed advancements and hope to more patients.”

Bladder cancer is the ninth most common cancer globally, with more than 614,000 new diagnoses each year, including approximately 85,000 cases in the United States. Muscle-invasive disease accounts for roughly 30% of all bladder cancer cases and carries a high risk of recurrence. Despite standard treatment with neoadjuvant cisplatin-based chemotherapy followed by surgery, approximately half of patients experience disease relapse after cystectomy.

Jeff Legos, PhD, MBA, Chief Oncology Officer, Pfizer, said “For the first time, patients with muscle-invasive bladder cancer are seeing significant survival benefits from combination therapy in a perioperative setting without the need for platinum-based chemotherapy, signaling the potential for a new standard of care for this community. The EV-304 results, combined with the recent unprecedented results from the EV-303 trial, showcase the promising future of this regimen as a cornerstone of care for bladder cancer regardless of cisplatin eligibility.”

PADCEV plus pembrolizumab is not currently approved as neoadjuvant and adjuvant therapy for cisplatin-eligible patients with MIBC. The companies plan to submit the EV-304 data for presentation at an upcoming medical congress and to engage with global regulatory authorities regarding potential regulatory filings. Notably, the combination was recently approved by the U.S. FDA for neoadjuvant and adjuvant treatment in cisplatin-ineligible patients with MIBC based on results from the Phase III EV-303 (KEYNOTE-905) trial.