Astellas and Pfizer Announce Positive Phase 3 Trial Results for PADCEV and KEYTRUDA Combination in Muscle-Invasive Bladder Cancer

Astellas Pharma and Pfizer announced positive results from the pivotal Phase 3 EV-303 clinical trial for PADCEV in combination with KEYTRUDA for muscle-invasive bladder cancer. The combination significantly improved event-free survival and overall survival compared to surgery alone. Results will be presented at the European Society of Medical Oncology Congress in Berlin, Germany.

Astellas Pharma Inc. and Pfizer Inc. have announced positive results from the pivotal Phase 3 EV-303 clinical trial for PADCEV (enfortumab vedotin) in combination with KEYTRUDA (pembrolizumab) for muscle-invasive bladder cancer (MIBC). The combination therapy demonstrated significant improvements in event-free survival (EFS) and overall survival (OS) compared to surgery alone.

The study, also known as KEYNOTE-905, evaluated the combination in patients with MIBC who were ineligible for or declined cisplatin-based chemotherapy. The primary endpoint of EFS showed a 60% reduction in the risk of tumor recurrence, progression, or death for patients treated with neoadjuvant and adjuvant PADCEV plus KEYTRUDA compared to surgery alone (Hazard Ratio (HR) of 0.40; 95% Confidence Interval (CI), 0.28-0.57; p0.0001). The estimated median EFS has not yet been reached for the combination arm versus 15.7 months for the surgery alone arm.

The estimated median OS has not yet been reached for the combination arm versus 41.7 months for the surgery arm. An estimated 74.7% of patients treated with the combination were event-free at two years, relative to 39.4% of patients who received surgery only. The combination therapy also demonstrated a 57.1% pathologic complete response (pCR) rate versus an 8.6% pCR rate for patients who received surgery only (estimated difference 48.3%; 95% CI 39.5-56.5; p0.000001).

The results from the EV-303 trial will be presented in a Presidential Symposium (Abstract #LBA2) at the 2025 European Society of Medical Oncology (ESMO) Congress in Berlin, Germany. Consistent EFS and OS benefits were seen across all pre-defined subgroups, including age, gender, smoking status, PD-L1 status, and protocol-defined stratification groups based on cisplatin ineligibility.

The safety profile of the combination was consistent with previously reported data, with the most common adverse events (AEs) including pruritus (itching), alopecia, diarrhea, fatigue, and anemia. Grade 3 AEs due to any cause occurred in 71.3% of patients treated in the combination arm and 45.9% of patients who received surgery only.

PADCEV plus KEYTRUDA is not currently approved for use as neoadjuvant and adjuvant treatment in cisplatin-ineligible patients with MIBC. The companies plan to discuss these results with global health authorities for potential regulatory filings.

Astellas Pharma and Pfizer are also evaluating the combination in cisplatin-eligible patients with MIBC in the EV-304 Phase 3 clinical trial (also known as KEYNOTE-B15).