Merck said the European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion recommending approval of KEYTRUDA (pembrolizumab) in combination with Padcev (enfortumab vedotin-ejfv) as perioperative treatment for adults with resectable muscle‑invasive bladder cancer who are ineligible for cisplatin‑containing chemotherapy. The regimen would be given as neoadjuvant therapy and then continued after radical cystectomy as adjuvant treatment, and the opinion also covers the subcutaneous formulation KEYTRUDA SC (KEYTRUDA QLEX in the U.S.). A final decision from the European Commission, which will apply in the European Union, Iceland, Liechtenstein and Norway, is expected by the third quarter of 2026.
The recommendation is based on results from the Phase 3 KEYNOTE‑905 (EV‑303) trial, conducted with Pfizer and Astellas, in which perioperative KEYTRUDA plus Padcev improved event‑free survival, overall survival and pathologic complete response compared with surgery alone in cisplatin‑ineligible or cisplatin‑declining patients with muscle‑invasive bladder cancer. The combination reduced the risk of event‑free survival events by 60% versus surgery alone, with a hazard ratio of 0.40 (95% CI, 0.28–0.57; p<0.0001); median event‑free survival was not reached for the combination (95% CI, 37.3–not reached) versus 15.7 months (95% CI, 10.3–20.5) for surgery alone. The regimen also reduced the risk of death by 50% (HR 0.50 [95% CI, 0.33–0.74]; p=0.0002), with median overall survival not reached for the combination (95% CI, not reached–not reached) versus 41.7 months (95% CI, 31.8–not reached) with surgery alone.
KEYNOTE‑905 also showed a higher pathologic complete response rate with the combination than with surgery alone. Pathologic complete response was 57.1% (95% CI, 49.3–64.6) with KEYTRUDA plus Padcev compared with 8.6% (95% CI, 4.9–13.8) in the surgery‑alone arm (p<0.0001). Full results were presented during a Presidential Symposium at the European Society for Medical Oncology Congress 2025 and published in The New England Journal of Medicine.
“Patients in Europe with resectable muscle‑invasive bladder cancer who are ineligible for cisplatin‑containing chemotherapy have limited treatment options and are at high risk for disease recurrence,” said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. She said the positive opinion moves the company closer to offering a KEYTRUDA‑based regimen before and after surgery for these patients, citing the KEYNOTE‑905 data.
Merck noted that KEYTRUDA and KEYTRUDA QLEX in combination with Padcev were previously approved in November 2025 by the U.S. Food and Drug Administration as neoadjuvant and adjuvant treatment for adults with muscle‑invasive bladder cancer who are ineligible for cisplatin‑based chemotherapy.
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