Collectively, the data suggest that perioperative Padcev plus Keytruda may offer consistent survival benefits across both cisplatin-eligible and -ineligible patient groups, reinforcing its potential as a new standard of care.
News|Articles|April 20, 2026
FDA Grants Priority Review for Padcev Plus Keytruda in Bladder Cancer Treatment
Author(s)Emily Schoenthaler
Listen
0:00 / 0:00
Key Takeaways
- FDA Priority Review targets perioperative enfortumab vedotin plus pembrolizumab for MIBC irrespective of cisplatin eligibility, with a regulatory action date of August 17, 2026.
- EV-304 met the primary endpoint, delivering statistically significant, clinically meaningful event-free survival improvement versus standard neoadjuvant gemcitabine/cisplatin, with additional overall survival gains.
The FDA has granted Priority Review to the combination of Padcev and Keytruda as a perioperative treatment for muscle-invasive bladder cancer, with a decision expected by Aug. 2026. Phase 3 trial results showed the regimen significantly improves survival outcomes and could become a new standard of care regardless of cisplatin eligibility.
Advertisement
Astellas Pharma and Pfizer have secured Priority Review designation from the FDA for a supplemental biologics license application seeking to expand the use of Padcev (enfortumab vedotin-ejfv) in combination with Keytruda (pembrolizumab) as a perioperative treatment for patients with muscle-invasive bladder cancer (MIBC), regardless of cisplatin eligibility. The regulatory decision is expected by Aug. 17, 2026.
Phase 3 Data Demonstrate Survival Benefit
The application is supported by results from the Phase 3 EV-304 (KEYNOTE-B15) trial, a randomized study evaluating the combination regimen administered before and after surgery compared with standard neoadjuvant
chemotherapy. The study met its primary endpoint, demonstrating statistically significant and clinically meaningful improvements in event-free survival, with additional gains observed in overall survival.1
Specifically, the combination reduced the risk of tumor recurrence, progression, or death by 47% compared with gemcitabine and cisplatin chemotherapy, and lowered the risk of death by 35%.2 The regimen also showed a markedly higher pathological complete response rate—55.8% versus 32.5%—indicating that more than half of treated patients had no detectable disease at the time of surgery.3
Expanding Beyond Cisplatin Eligibility
The EV-304 findings build on earlier Phase 3 data from the EV-303 trial in cisplatin-ineligible patients, which supported a prior FDA approval of the combination in that population. Collectively, the data suggest that perioperative Padcev plus Keytruda may offer consistent survival benefits across both cisplatin-eligible and -ineligible patient groups, reinforcing its potential as a new standard of care.4
MIBC remains a challenging disease with high rates of recurrence despite curative-intent surgery, with approximately half of patients experiencing disease return following treatment. The current standard of care typically involves cisplatin-based chemotherapy followed by cystectomy, but not all patients are eligible for platinum-based regimens due to toxicity concerns or comorbidities.
Mechanism and Clinical Context
The investigational combination offers a potential alternative that may reduce reliance on chemotherapy. Padcev, an antibody-drug conjugate targeting Nectin-4, delivers a cytotoxic payload directly to cancer cells, while Keytruda, a PD-1 inhibitor, enhances immune-mediated tumor response. Together, the agents are designed to provide both targeted and immunologic mechanisms of action.
Safety and Regulatory Outlook
Safety findings from EV-304 were consistent with the known profiles of the individual therapies, with no new safety signals identified. The trial enrolled more than 800 patients and evaluated both neoadjuvant and adjuvant use of the regimen in conjunction with surgery.5
Regulatory submissions based on these data are also under review in other global markets, reflecting growing momentum behind the combination. If approved in the United States for all eligible patients, the regimen would become the first perioperative therapy for MIBC that is not limited by cisplatin eligibility, potentially reshaping treatment paradigms in earlier-stage bladder cancer.
References
1. PADCEV™ Plus Keytruda® Significantly Improves Survival for Patients with Muscle-Invasive Bladder Cancer Regardless of Cisplatin Eligibility. (2025 Dec. 17). Astellas.com.
2. Liu, A. (2026 Feb. 27). Padcev-Keytruda combo aces another bladder cancer trial as MIBC landscape becomes more complex. FiercePharma.com.
3. PADCEV™ + Keytruda® Cuts Risk of Recurrence or Death by Nearly 50% in Cisplatin-Eligible Muscle-Invasive Bladder Cancer. (2026 Feb. 27). Astellas.com.
4. PADCEV™ Plus Keytruda® Significantly Improves Survival for Patients with Muscle-Invasive Bladder Cancer Regardless of Cisplatin Eligibility (2025 Dec. 17). SeekingAlpha.com.
5. KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 47% and Risk of Death by 35% for Cisplatin-Eligible Patients with Muscle-Invasive Bladder Cancer When Given Before and After Surgery. (2026 Feb. 27). Merck.com.
Advertisement
Related Content
Advertisement
Advertisement
Advertisement