Astellas Pharma and Pfizer have reported positive topline results from an interim analysis of the Phase 3 EV-304 clinical trial, strengthening evidence that the combination of PADCEV™ (enfortumab vedotin) and Keytruda® (pembrolizumab) could redefine treatment for patients with muscle-invasive bladder cancer (MIBC). The study, also known as KEYNOTE-B15, evaluated the antibody-drug conjugate and immunotherapy combination as neoadjuvant and adjuvant therapy compared with standard cisplatin-based chemotherapy in patients eligible for platinum treatment.
The trial met its primary endpoint, demonstrating clinically meaningful and statistically significant improvements in event-free survival. Importantly, the study also achieved a key secondary endpoint of overall survival, marking a notable advance in a disease area where long-term outcomes have historically remained poor despite aggressive treatment. Investigators also reported a significant improvement in the rate of pathologic complete response among patients who received PADCEV plus pembrolizumab before surgery, compared with those who received neoadjuvant chemotherapy.
Muscle-invasive bladder cancer accounts for roughly 30 percent of all bladder cancer cases and is associated with a high risk of recurrence and progression. Even with current standard treatment—neoadjuvant cisplatin-based chemotherapy followed by surgery—around half of patients experience disease recurrence after cystectomy. The EV-304 findings suggest that a perioperative approach combining PADCEV and pembrolizumab could offer a more effective alternative to platinum-based regimens.
Christopher Hoimes, director of the Bladder Cancer Program at Duke Cancer Institute and a principal investigator in the EV-304 study, described the results as a milestone in urothelial cancer treatment. He noted that nearly half of patients with MIBC progress to metastatic disease within three years of diagnosis, underscoring the need for more effective strategies. According to Hoimes, the combined results from EV-303 and EV-304 indicate that perioperative enfortumab vedotin plus pembrolizumab can deliver significant survival benefits across both cisplatin-eligible and cisplatin-ineligible patient populations.
Astellas highlighted the broader implications of the findings, emphasizing that they build on recent regulatory progress in the United States. Moitreyee Chatterjee-Kishore, head of oncology development at Astellas, said the EV-304 data reinforce the potential of the combination regimen to improve outcomes for a wide range of patients with MIBC, regardless of cisplatin eligibility. She added that the results strengthen the overall evidence base supporting PADCEV plus pembrolizumab as a future treatment option across disease stages.
Pfizer executives echoed that sentiment, pointing to the potential shift away from traditional platinum-based chemotherapy. Jeff Legos, Pfizer’s chief oncology officer, said the EV-304 results represent the first time combination therapy in a perioperative setting has delivered significant survival benefits without relying on platinum chemotherapy. He described the regimen as a promising cornerstone for bladder cancer care.
The safety profile of PADCEV plus pembrolizumab in EV-304 was consistent with the known safety characteristics of the combination, with no new safety concerns reported. The companies plan to present the full data set at an upcoming medical congress and to engage with global health authorities regarding potential regulatory filings.
While PADCEV plus pembrolizumab is already approved in the U.S. for cisplatin-ineligible patients with MIBC based on the Phase 3 EV-303 trial, it is not yet approved for perioperative use in cisplatin-eligible patients. The latest results, however, suggest the combination could soon play a central role in reshaping the standard of care for muscle-invasive bladder cancer worldwide.