-Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”)  announced positive results from the Phase 3 EV-304 clinical trial (also known as KEYNOTE-B15) for PADCEV^TM (enfortumab vedotin), a Nectin-4 directed antibody-drug conjugate, in combination with Keytruda^® (pembrolizumab), a PD-1 inhibitor, in patients with muscle-invasive bladder cancer (MIBC) eligible for cisplatin-based chemotherapy. Perioperative (before and after surgery) enfortumab vedotin plus pembrolizumab demonstrated a 47% reduction in the risk of tumor recurrence, progression or death compared to patients treated with standard of care neoadjuvant (before surgery) gemcitabine and cisplatin (Hazard Ratio (HR) of 0.53; 95% Confidence Interval (CI), 0.41–0.70; 1-sided p<.0001).ⁱ An estimated 79.4% of patients were event-free at two years, relative to 66.2% treated with standard of care neoadjuvant chemotherapy.ⁱ These data will be presented today in an oral session (Abstract #LBA630) and were featured in the press program at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco, CA. They will also be discussed with global health authorities for potential regulatory filings.

Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, and an EV-304 Principal Investigator

“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."

Overall survival was a key secondary endpoint in EV-304 and showed a 35% reduced risk of death in patients treated with perioperative enfortumab vedotin plus pembrolizumab versus neoadjuvant chemotherapy (HR of 0.65; 95% CI, 0.48-0.89; 1-sided p=.0029).ⁱ The combination also demonstrated a pathological complete response (pCR) rate of 55.8% compared with 32.5% pCR rate at the time of surgery (estimated difference 23.4%; 95% CI, 16.7-29.8; 1-sided p<.0001), indicating that more than half of patients treated with the combination had no detectable disease at the time of surgery.ⁱ EFS, OS and pCR benefits were generally consistent across all pre-defined subgroups, including age, gender, PD-L1 status, clinical stage and geographic region.ⁱ

The safety profile for perioperative enfortumab vedotin plus pembrolizumab observed in EV-304 was consistent with prior experience with the combination and there were no new safety signals. Grade ≥3 adverse events (AEs) due to any cause occurred in 75.7% of patients treated with perioperative enfortumab vedotin plus pembrolizumab compared to 67.2% of patients treated with neoadjuvant chemotherapy.ⁱ

Jeff Legos, PhD, MBA, Chief Oncology Officer, Pfizer

“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.”

Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas

“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.”

Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 patients each year globally, including an estimated 85,000 people in the U.S.ⁱⁱ,ⁱⁱⁱ MIBC represents approximately 30% of all bladder cancer cases.^iv Even after undergoing curative intent surgery, half of patients with MIBC experience disease recurrence.^v

PADCEV plus pembrolizumab is not currently approved for use as perioperative treatment in cisplatin-eligible patients with MIBC. PADCEV plus pembrolizumab was approved in November 2025 by the U.S. FDA for use as perioperative treatment in cisplatin-ineligible patients with MIBC, based on results from the EV-303 Phase 3 clinical trial (also known as KEYNOTE-905).

The EV-304 trial is an ongoing, open-label, randomized, controlled, Phase 3 study evaluating neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab versus neoadjuvant chemotherapy (gemcitabine and cisplatin) in patients with MIBC who are eligible for cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant PADCEV in combination with pembrolizumab (arm A) or neoadjuvant chemotherapy (arm B). Curative-intent surgery (cystectomy) was performed in both arms. Enfortumab vedotin in combination with pembrolizumab was administered as a planned total of 9 cycles of enfortumab vedotin and 17 cycles of pembrolizumab split before and after surgery.^vi

The primary endpoint of this trial is EFS, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy (RC) or failure to undergo RC in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause. Key secondary endpoints include OS and pCR rate.^vi