SILVER SPRING, Maryland, July 10, 2026
Merck has received U.S. Food and Drug Administration (FDA) approval for Keytruda® (pembrolizumab) or Keytruda Qlex® (pembrolizumab and berahyaluronidase alfa-pmph), each in combination with Astellas Pharma’s Padcev® (enfortumab vedotin-ejfv), as perioperative treatment for adults with muscle invasive bladder cancer (MIBC) undergoing radical cystectomy. The approval significantly expands the previous indication from patients who were cisplatin-ineligible to all patients with MIBC who are candidates for bladder removal surgery, representing a major advancement in bladder cancer treatment. The decision is based on positive results from the Phase III KEYNOTE-B15/EV-304 clinical trial, which demonstrated significant improvements in survival outcomes compared with conventional chemotherapy. The expanded approval further strengthens the role of immunotherapy combined with antibody-drug conjugate therapy as a new standard of care for patients with high-risk urothelial cancer while reinforcing the growing importance of precision oncology in improving long-term patient outcomes.
Phase III KEYNOTE-B15 Trial Demonstrates Superior Clinical Outcomes
The FDA approval was supported by findings from the KEYNOTE-B15/EV-304 Phase III randomized, multicenter study, which enrolled 808 previously untreated patients with muscle invasive bladder cancer eligible for radical cystectomy and cisplatin-based chemotherapy. Patients received either perioperative Keytruda combined with Padcev or the standard neoadjuvant regimen of gemcitabine and cisplatin before surgery. The study demonstrated a statistically significant improvement in event-free survival (EFS), with median EFS not reached in the Keytruda plus Padcev arm compared with 48.5 months in the chemotherapy group, reducing the risk of disease recurrence, progression, or death by 47%. The combination therapy also achieved a 35% reduction in the risk of death, demonstrating a significant overall survival benefit over standard chemotherapy. The safety profile remained consistent with previous studies, with manageable adverse events and no unexpected safety concerns, further supporting the clinical value of combining PD-1 immune checkpoint inhibition with antibody-drug conjugate technology for patients with aggressive bladder cancer.
Expanded Approval Strengthens Precision Oncology Treatment Strategy
The newly approved regimen includes four cycles of neoadjuvant Keytruda and Padcev administered before surgery, followed by adjuvant combination therapy and continued Keytruda maintenance treatment after radical cystectomy. The approval was granted under the FDA’s Project Orbis, an international initiative that enables concurrent regulatory review of innovative oncology medicines with global health authorities, including agencies in Australia, Canada, Switzerland, the United Kingdom, and Israel. The application also received Priority Review and was approved five weeks ahead of the FDA target action date, reflecting the urgent need for more effective treatment options for patients with muscle invasive bladder cancer.
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By extending eligibility beyond cisplatin-ineligible patients, the FDA has expanded access to a highly effective perioperative immunotherapy regimen capable of reducing recurrence and improving survival following surgery. The approval further reinforces Merck’s leadership in oncology, while highlighting the continued success of combining Keytruda with Padcev to advance precision cancer care, improve treatment outcomes, and establish a new benchmark in the management of muscle invasive bladder cancer.
Source: Merck press release
