NEW YORK & TOKYO — Pfizer Inc. and Astellas Pharma Inc. reported positive results from the Phase 3 EV-304 clinical trial, also known as KEYNOTE-B15, showing that PADCEV (enfortumab vedotin) in combination with Keytruda (pembrolizumab) significantly reduced the risk of tumor recurrence, progression, or death in patients with cisplatin-eligible muscle-invasive bladder cancer.
Perioperative treatment with enfortumab vedotin plus pembrolizumab — administered before and after surgery — reduced the risk of recurrence, progression, or death by 47% compared with standard neoadjuvant gemcitabine and cisplatin chemotherapy (Hazard Ratio 0.53; 95% Confidence Interval 0.41–0.70; 1-sided p<.0001). An estimated 79.4% of patients treated with the combination were event-free at two years, compared with 66.2% of those receiving standard chemotherapy.
Overall survival, a key secondary endpoint, showed a 35% reduction in the risk of death with the combination therapy (HR 0.65; 95% CI 0.48–0.89; 1-sided p=.0029). The regimen also achieved a pathological complete response rate of 55.8%, compared with 32.5% for chemotherapy alone, meaning more than half of patients had no detectable disease at the time of surgery.
“Approximately half of patients with muscle-invasive bladder cancer experience disease recurrence even after having their bladder removed. The EV-304 results, combined with the EV-303 study, provide compelling evidence that perioperative enfortumab vedotin plus pembrolizumab may offer survival benefits in the curative setting for patients with muscle-invasive bladder cancer, highlighting a potential departure from platinum-based chemotherapy as a cornerstone of care,” said Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute and an EV-304 principal investigator.
The safety profile of the combination was consistent with prior studies, and no new safety signals were identified. Grade 3 or higher adverse events occurred in 75.7% of patients treated with the combination compared with 67.2% of those receiving neoadjuvant chemotherapy.
“For people with muscle-invasive bladder cancer, a perioperative approach that avoids the need for platinum-based chemotherapy has demonstrated significant survival benefits. These compelling data, reinforced by the unprecedented EV-303 results, suggest a transformative opportunity to establish PADCEV plus pembrolizumab as the next standard of care if approved, and provide a meaningful step forward for patients and their families,” said Jeff Legos, PhD, MBA, Chief Oncology Officer at Pfizer.
“The EV-304 study data further substantiate the role of enfortumab vedotin plus pembrolizumab in bladder cancer and demonstrate its potential to offer patients with muscle-invasive bladder cancer more time with their loved ones. We are delighted with these new data and remain committed to investigating therapies for challenging and hard-to-treat cancers, with a goal of bringing renewed hope to patients,” said Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development at Astellas.
Bladder cancer is the ninth most common cancer worldwide, with more than 614,000 new cases diagnosed annually, including an estimated 85,000 in the U.S. Muscle-invasive disease accounts for roughly 30% of all bladder cancer cases, and about half of patients experience recurrence even after curative-intent surgery.
PADCEV plus pembrolizumab is not currently approved as perioperative treatment for cisplatin-eligible patients with muscle-invasive bladder cancer. The combination was approved in November 2025 by the U.S. Food and Drug Administration for perioperative use in cisplatin-ineligible patients based on results from the EV-303 Phase 3 trial.
