EC approves Keytruda plus Padcev as perioperative treatment for muscle-invasive bladder cancer – Merck
Merck, known as MSD outside of the United States and Canada, announced the European Commission has approved KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with Padcev (enfortumab vedotin-ejfv), as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment for adults with resectable muscle-invasive bladder cancer (MIBC).
This approval, which also covers KEYTRUDA SC [known as KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) in the U.S.], marks the first and only PD-1 inhibitor plus antibody-drug conjugate (ADC) regimen available for patients with MIBC regardless of cisplatin eligibility in the European Union (EU).
“Although cisplatin-based chemotherapy has been a standard treatment approach for many patients with muscle-invasive bladder cancer, recurrence remains a significant challenge,” said Dr. Alfonso Gómez de Liaño, Hospital Universitario Insular de Gran Canaria, and KEYNOTE-B15 primary investigator. “Based on results from the KEYNOTE-B15 trial, today’s approval is a meaningful advance for patients with muscle-invasive bladder cancer in the European Union, extending this chemotherapy-free perioperative treatment option to patients regardless of cisplatin eligibility.”
“Building on the previous approval of KEYTRUDA plus Padcev in the European Union less than six months ago, we’re pleased to bring this important treatment option to a broader patient population as the first PD-1 inhibitor plus antibody-drug conjugate regimen approved for people with muscle-invasive bladder cancer regardless of cisplatin eligibility,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “This approval represents encouraging progress in bladder cancer care and underscores our commitment to addressing the needs of people who are living with this disease.”
The EC approval is based on results from the Phase 3 KEYNOTE-B15 trial (also known as EV-304), which was conducted in collaboration with Pfizer and Astellas. In the study, KEYTRUDA plus Padcev, as perioperative treatment, demonstrated a statistically significant improvement in event-free survival (EFS), reducing the risk of EFS events (defined as disease progression, recurrence or death) by 47% (HR=0.53 [95% CI, 0.41-0.70]; p<0.0001; 87/405 [21%] versus 146/403 [36%]) in patients with MIBC who are eligible for cisplatin-based chemotherapy compared to neoadjuvant chemotherapy (gemcitabine and cisplatin) and surgery. KEYTRUDA plus Padcev also demonstrated a statistically significant improvement in overall survival (OS), reducing the risk of death by 35% (HR=0.65 [95% CI, 0.48-0.89]; p=0.0029; 69/405 [17%] versus 99/403 [25%]) in these patients when compared to neoadjuvant chemotherapy and surgery. The trial showed KEYTRUDA plus Padcev demonstrated a statistically significant improvement in pathologic complete response (pCR) rate compared to neoadjuvant chemotherapy (55.8% [95% CI: 50.8, 60.7] versus 32.5% [95% CI: 28.0, 37.3]; p<0.0001). The approval follows a positive recommendation issued by the European Medicines Agency’s Committee for Medicinal Products for Human Use in September 2026.
This approval authorizes marketing of this KEYTRUDA treatment regimen for this indication in all 27 EU member states, as well as Iceland, Liechtenstein and Norway. Timing for commercial availability of KEYTRUDA for this indication in individual EU countries will depend on multiple factors, including the completion of national reimbursement procedures.
In July 2026, KEYTRUDA in combination with Padcev was approved by the FDA as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment for the treatment of adult patients with MIBC based on the Phase 3 KEYNOTE-B15 trial. This also represented the first and only PD-1 inhibitor plus ADC regimen approved in the U.S. for adults with MIBC regardless of cisplatin eligibility.
About KEYNOTE-B15
KEYNOTE-B15, also known as EV-304, is an open-label, randomized, multicenter, active-control Phase 3 trial (ClinicalTrials.gov, NCT04700124) evaluating perioperative KEYTRUDA in combination with Padcev and surgery (radical cystectomy [RC] and pelvic lymph node dissection [PLND]) versus neoadjuvant chemotherapy (gemcitabine plus cisplatin) and surgery in patients with previously untreated MIBC who are eligible for cisplatin-based chemotherapy. The trial enrolled 808 patients who were randomized 1:1 to receive either:
i) Neoadjuvant KEYTRUDA 200 mg intravenously on Day 1 and Padcev 1.25 mg/kg intravenously on Days 1 and 8 of each 21-day cycle for four cycles prior to surgery, followed by adjuvant KEYTRUDA 200 mg on Day 1 of each 21-day cycle for 13 cycles and adjuvant Padcev 1.25 mg/kg on Days 1 and 8 of each 21-day cycle for five cycles (n=405), or;
iii) Neoadjuvant gemcitabine 1000 mg/m 2 on Days 1 and 8 and cisplatin 70 mg/m 2 on Day 1 of each 21-day cycle for four cycles prior to surgery, followed by observation (n=403).
The major efficacy outcome measure was EFS as assessed by blinded independent central review (BICR), defined as the time from randomization to the first occurrence of the following events: disease progression preventing curative surgery, failure to undergo surgery for participants with muscle invasive residual disease, incomplete surgical resection, local or distant recurrence after surgery or death. Additional efficacy outcome measures were OS and pCR rate as assessed by blinded independent pathology review.
