Astellas Pharma has submitted a supplemental New Drug Application in Japan for PADCEV (enfortumab vedotin) plus Keytruda (pembrolizumab) as perioperative treatment for cisplatin-eligible muscle-invasive bladder cancer, supported by Phase 3 EV-304/KEYNOTE-B15.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
Astellas Pharma announced the submission of a supplemental New Drug Application (sNDA) to Japan’s Ministry of Health, Labour and Welfare (MHLW) seeking approval for PADCEV (enfortumab vedotin) in combination with Keytruda (pembrolizumab) as perioperative treatment for adults with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-containing chemotherapy.
The proposed perioperative regimen includes neoadjuvant treatment before radical cystectomy followed by continued adjuvant therapy after surgery. The application is supported by results from the Phase 3 EV-304 trial, also known as KEYNOTE-B15 (NCT04700124), which compared perioperative enfortumab vedotin plus pembrolizumab against standard neoadjuvant gemcitabine and cisplatin chemotherapy in cisplatin-eligible MIBC patients.
Event-free survival (EFS) was the primary endpoint of the study, while overall survival (OS) and pathological complete response (pCR) rate were key secondary endpoints. In the EFS analysis, the combination regimen reduced the risk of tumor recurrence, progression, or death by 47% compared with standard chemotherapy. In the OS analysis, the regimen demonstrated a 35% reduction in the risk of death. Results from EV-304 were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).
The safety profile of enfortumab vedotin plus pembrolizumab was consistent with prior experience with the combination, with no unexpected toxicities observed in the perioperative setting. No new safety signals were identified in the trial. The most common treatment-related adverse events occurring in at least 30% of patients included pruritus, alopecia, diarrhea, and anemia.
Bladder cancer is the ninth most commonly diagnosed cancer in Japan, with an estimated 25,900 new cases expected in 2025. Muscle-invasive disease accounts for around 30% of bladder cancer cases. Despite curative-intent surgery, recurrence rates remain high in MIBC, underscoring the need for more effective perioperative treatment strategies.
PADCEV is a Nectin-4-directed antibody-drug conjugate designed to deliver the microtubule-disrupting agent monomethyl auristatin E (MMAE) directly into cancer cells expressing Nectin-4, a protein highly expressed in bladder cancer. The drug is already approved in several countries, including the United States and Japan, for certain patients with locally advanced or metastatic urothelial cancer in combination with pembrolizumab or as monotherapy in previously treated settings.
The EV-304/KEYNOTE-B15 study is an ongoing, randomized, open-label Phase 3 trial evaluating perioperative enfortumab vedotin plus pembrolizumab versus neoadjuvant gemcitabine and cisplatin chemotherapy in patients with MIBC who are eligible for cisplatin-based chemotherapy. Curative-intent surgery was performed in both treatment arms.
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About the Writer
Samiksha Vikram Jadhav (LinkedIn) is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.