- First and only treatment regimen for adults with MIBC, regardless of cisplatin eligibility, representing a platinum-free potential standard of care
- Broadened approval supported by Phase 3 EV-304 data showing a nearly 50% reduction in the risk of tumor recurrence, progression or death, and a 35% reduction in the risk of death, versus standard of care in cisplatin-eligible patients
The approval was based on results from the pivotal Phase 3 EV-304 clinical trial (also known as KEYNOTE-B15), which were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU). This expanded indication builds on the November 2025 U.S. FDA approval of the combination for use as neoadjuvant and adjuvant treatment in cisplatin-ineligible adult patients with MIBC, based on results from the EV-303 Phase 3 clinical trial (also known as KEYNOTE-905) that were published in the New England Journal of Medicine.
Christopher Hoimes, DO, Director of the Bladder Cancer Program and Center for Cancer Immunotherapy at Duke Cancer Institute, and an EV-304 Principal Investigator “For muscle-invasive bladder cancer, a comprehensive treatment approach is important; the neoadjuvant phase can help shrink the tumor and target undetectable cancer cells early before surgery, while the adjuvant phase can be critical in eliminating residual, undetectable cancer cells following surgery. These data from EV-304 and this approval show that by delivering this regimen across both the neoadjuvant and adjuvant phases, without platinum-based chemotherapy, we can significantly reduce the risk of recurrence and improve overall survival — offering a potential new standard of care for adult patients with muscle-invasive bladder cancer.”Aamir Malik, Executive Vice President, Chief U.S. Commercial Officer, Pfizer
“Today’s approval marks a historic turning point for the treatment of muscle-invasive bladder cancer, providing adult patients with the first approved platinum-free combination regimen shown to significantly improve survival over the current standard of care – regardless of cisplatin-eligibility. PADCEV plus pembrolizumab has established itself as the standard of care for first line therapy of advanced stages of bladder cancer, and we’re thrilled to be able to provide this community a much-needed new treatment option in an earlier, potentially curative-intent setting.”
Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas
“The approval of neoadjuvant and adjuvant PADCEV plus pembrolizumab expands the established impact of this combination and represents a critical leap forward in how muscle-invasive bladder cancer can be treated. By delivering a clinically meaningful survival benefit, with profound event-free survival and pathological complete response rates, this regimen is the first platinum-free treatment option in nearly 25 years to outperform standard of care chemotherapy, offering new hope to patients living with this disease.”
In the EV-304 clinical trial, patients were randomized to receive surgery with neoadjuvant and adjuvant PADCEV plus pembrolizumab or surgery with neoadjuvant chemotherapy. PADCEV plus pembrolizumab was administered as a planned total of 9 cycles of PADCEV and 17 cycles of pembrolizumab split before and after surgery.ii PADCEV plus pembrolizumab demonstrated:
- A 47% reduction in the risk of tumor recurrence, progression or death compared to patients treated with standard of care neoadjuvant gemcitabine and cisplatin (Hazard Ratio (HR) of 0.53; 95% Confidence Interval (CI), 0.41–0.70; 1-sided p<0.0001).ii
- An estimated 79.4% of patients were event-free at two years, compared with 66.2% treated with standard of care.ii
- A 35% reduction in the risk of death compared to neoadjuvant chemotherapy (HR of 0.65; 95% CI, 0.48-0.89; 1-sided p=0.0029).ii
- A pathological complete response (pCR) rate of 55.8% compared with 32.5% with chemotherapy at the time of surgery (estimated difference 23.4%; 95% CI 16.7-29.8; 1-sided p<0.0001).ii
- A safety profile consistent with prior experience with this combination, and no new identifiable safety signals. Grade ≥3 adverse events (AEs) due to any cause occurred in 75.7% of patients treated with neoadjuvant and adjuvant PADCEV plus pembrolizumab compared to 67.2% of patients treated with neoadjuvant chemotherapy.ii
- PADCEV [package insert]. Northbrook, IL: Astellas Pharma US, Inc.
- National Institute of Health. National Library of Medicine. Perioperative Enfortumab Vedotin (EV) Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Chemotherapy for Cisplatin-Eligible Muscle Invasive Bladder Cancer (MIBC) (MK-3475-B15/ KEYNOTE-B15 / EV-304) (KEYNOTE-B15). ClinicalTrials.gov identifier: NCT04700124. Published January 7, 2021. Updated August 26, 2025. Accessed February 24, 2026. Available at:https://www.clinicaltrials.gov/study/NCT04700124.