- Approval based on Phase 3 EV-303 results demonstrating significant improvements in event-free survival and overall survival compared with surgery alone -
- Despite curative-intent surgery, patients with muscle-invasive bladder cancer continue to face a substantial risk of disease recurrence -
TOKYO, June 24, 2026 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced that the European Commission has granted Marketing Authorization for PADCEVTM (enfortumab vedotin), in combination with Keytruda® (pembrolizumab), as neoadjuvant treatment (before surgery) and then continued after radical cystectomy (surgery) as adjuvant treatment, for adults with resectable muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy in the European Union (EU). The approval establishes the first and only approved perioperative (neoadjuvant and adjuvant) treatment option for this patient population in the EU.
The approval is based on results from the Phase 3 EV-303 clinical trial (KEYNOTE-905), in which perioperative enfortumab vedotin plus pembrolizumab significantly improved Event-Free Survival (EFS) and Overall Survival (OS) compared with surgery alone in patients with MIBC who were ineligible for or declined cisplatin-containing chemotherapy.1 The combination reduced the risk of tumor recurrence, progression, or death by 60% (Hazard Ratio (HR) 0.40, 95% CI, 0.28-0.57; p<0.0001)1 and reduced the risk of death by 50% (HR 0.50, 95% CI: 0.33-0.74; p=0.0002).1
The safety profile was consistent with the known profiles of the individual medicines, and no new safety signals were observed. The most common (≥30%) adverse events related to treatment with the combination were pruritus (itching), alopecia, diarrhea, fatigue, and anemia.1
Results from the trial were recently published in The New England Journal of Medicine.1
Moitreyee Chatterjee-Kishore, Ph.D., MBA, Executive Vice President and Head of Oncology Development, Astellas
“For patients with muscle-invasive bladder cancer who are unable to receive cisplatin-based chemotherapy, perioperative treatment options have historically been limited. This approval establishes the first approved perioperative treatment option for these patients in Europe and represents an important advance for patients facing this disease. We remain committed to improving outcomes for people living with bladder cancer through continued innovation across different stages of the disease.”
Christof Vulsteke, M.D., Ph.D., Head of Integrated Cancer Center Ghent (IKG, Belgium) and Clinical Trial Unit Oncology Ghent and EV-303 Principal Investigator
“Despite surgery with curative intent, many patients with muscle-invasive bladder cancer experience disease recurrence. The EV-303 results demonstrated clinically meaningful improvements in both event-free and overall survival, supporting perioperative enfortumab vedotin plus pembrolizumab as an important new treatment option for cisplatin-ineligible patients in Europe.”
Alex Filicevas, Executive Director, World Bladder Cancer Patient Coalition
“For patients living with muscle-invasive bladder cancer, the possibility of the cancer returning after surgery can be a source of significant uncertainty and concern for them and their families. But patients who are unable to receive cisplatin-based chemotherapy have historically faced limited treatment options beyond surgery. This approval represents important progress for the bladder cancer community and a significant advance for patients affected by this disease.”
Bladder cancer remains a significant health burden across Europe, with nearly 200,000 people diagnosed each year.2 MIBC accounts for up to 30% of all bladder cancer cases.3 Up to half of patients with MIBC are ineligible to receive cisplatin-containing chemotherapy. Until now, there have been no approved perioperative treatment options for these patients, despite a substantial risk of disease recurrence following surgery.4
Enfortumab vedotin plus pembrolizumab is already approved in Europe as a first-line treatment for patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy.5 This approval expands the use of the combination into earlier-stage, resectable MIBC for patients who are ineligible for cisplatin-containing chemotherapy, extending its use from advanced disease into a curative-intent treatment setting.
Astellas is working closely with regulatory authorities and health technology assessment bodies across the European Union to support patient access following the approval.
Astellas has already reflected the impact of the EC approval in its financial forecast for the current fiscal year ending March 31, 2027.
About PADCEV (enfortumab vedotin)
PADCEV (enfortumab vedotin) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.6 Nonclinical data suggest the anticancer activity of enfortumab vedotin is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6
Enfortumab vedotin in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph is approved in the United States as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, for the treatment of adult patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy.
Additionally, enfortumab vedotin plus pembrolizumab is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) regardless of cisplatin eligibility in the United States, Japan, and a number of other countries around the world. In the European Union, the combination is approved for the treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy.
About the EV-303/KEYNOTE-905 Trial
The EV-303 trial (also known as KEYNOTE-905) is an ongoing, open-label, randomized, three-arm, controlled, Phase 3 study evaluating neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab or neoadjuvant and adjuvant pembrolizumab versus surgery alone in patients with MIBC who are either not eligible for or declined cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant pembrolizumab (arm A), surgery alone (arm B) or neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab (arm C). 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.
The primary endpoint of this trial is EFS between arm C and arm B, 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 imaging, blinded independent central review (BICR), and/or biopsy or death due to any cause. Key secondary endpoints include OS and pCR rate between arm C and arm B, as well as EFS, OS and pCR rate between arm A and arm B.
For more information on the global EV-303 trial, go to clinicaltrials.gov.
About Astellas
Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need.
About the Pfizer, Astellas and MSD Collaboration
Seagen and Astellas previously entered a clinical collaboration agreement with MSD to evaluate the combination of Seagen and Astellas’ PADCEV (enfortumab vedotin) and MSD’s KEYTRUDA (pembrolizumab) in patients with urothelial cancer. Pfizer Inc. successfully completed its acquisition of Seagen on December 14, 2023. KEYTRUDA is a registered trademark of MSD, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the United States and Canada).
References
1. Vulsteke C, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026;394(13):1257-1269.
2. European Association of Urology. Bladder Cancer: The Forgotten Cancer. Available at: https://uroweb.org/news/bladder-cancer-the-forgotten-cancer. Date Accessed: June 2026.
3. Bladder Cancer Awareness Network. What is Muscle Invasive Bladder Cancer? Available at: https://bcan.org/what-is-muscle-invasive-bladder-cancer/. Date Accessed: June 2026.
4. Squires P, et al. Treatment Patterns, Disease Recurrence, and Overall Survival in Patients with Muscle-Invasive Bladder Cancer after Radical Cystectomy: A Population-Level Claims-Based Analysis. Clinical Genitourinary Cancer. 2026;24(1):102466.
5. Masson-Lecomte, A. et al. EAU Guidelines on Upper Urinary Tract Urothelial Carcinoma. Available at: https://uroweb.org/guidelines/upper-urinary-tract-urothelial-cell-carcinoma. Date Accessed: June 2026.
6. Challita-Eid PM., et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 2016;76(10):3003-13.