On December 17, 2025 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported positive topline results from the Phase 3 KEYNOTE-B15 trial (also known as EV-304) in patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. The trial showed KEYTRUDA (pembrolizumab) plus Padcev (enfortumab vedotin-ejfv), given as neoadjuvant and adjuvant treatment (before and after surgery), demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS), overall survival (OS) and pathologic complete response (pCR) rates versus neoadjuvant chemotherapy and surgery.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The persistent risk of recurrence in cis-eligible patients with muscle-invasive bladder cancer, despite recent advances, underscores the continued need for effective perioperative treatments," said Dr. Matthew Galsky, Lillian and Howard Stratton Professor of Medicine, director of genitourinary medical oncology, Mount Sinai Tisch Cancer Center, and KEYNOTE-B15 principal study investigator. "The strength of these data demonstrates that pembrolizumab plus enfortumab vedotin—given before and after surgery—has the potential to significantly improve survival outcomes."
The trial, evaluating Merck’s KEYTRUDA, an anti-PD-1 therapy, plus Padcev, an antibody-drug conjugate (ADC), was conducted in collaboration with Pfizer and Astellas and builds on the clinical success of this combination in locally advanced or metastatic urothelial cancer (la/mUC) and cisplatin-ineligible MIBC.
"For people living with muscle-invasive bladder cancer, treatment decisions often need to be made earlier, when the opportunity to change the course of the disease is greatest," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "These results reinforce our conviction that moving KEYTRUDA into earlier stages of cancer care can make a meaningful difference for patients. By exploring combinations with ADCs in the perioperative setting, we aim to improve survival expectations for people facing muscle-invasive bladder cancer."
The safety profile of KEYTRUDA plus Padcev in this study was consistent with the known safety profiles of each agent. No new safety signals were identified with the combination. The companies plan to share these results with regulatory authorities worldwide for potential regulatory filings and will present the data at an upcoming medical meeting.
KEYTRUDA plus Padcev is currently approved for the treatment of adult patients with la/mUC in the U.S., the European Union (EU), Japan and several other countries around the world. KEYTRUDA plus Padcev is also approved in the U.S. for the treatment of adult patients with MIBC who are ineligible for cisplatin-based chemotherapy. KEYTRUDA as monotherapy is also approved in the U.S., EU, Japan and other countries for the treatment of certain patients with la/mUC or a type of non-muscle-invasive bladder cancer (NMIBC).
Three additional Phase 3 studies are currently evaluating KEYTRUDA across all stages of bladder cancer, including non-muscle-invasive, muscle-invasive and metastatic. Two of these studies are in MIBC including KEYNOTE-866 (NCT03924856) and KEYNOTE-992 (NCT04241185). KEYTRUDA is also being evaluated in combination with Bacillus Calmette-Guerin (BCG) in patients with NMIBC in KEYNOTE-676 (NCT03711032).
About KEYNOTE-B15/EV-304
KEYNOTE-B15, also known as EV-304, is an open-label, randomized Phase 3 trial (ClinicalTrials.gov, NCT04700124) evaluating perioperative KEYTRUDA in combination with Padcev and surgery (radical cystectomy and pelvic lymph node dissection) versus neoadjuvant chemotherapy (gemcitabine plus cisplatin) and surgery in patients with MIBC who are cisplatin-eligible. The trial enrolled 808 patients who were randomized to receive either:
Four cycles (each cycle length is 21 days) of neoadjuvant KEYTRUDA intravenous (IV) infusion plus enfortumab vedotin IV infusion, followed by surgery, followed by 13 cycles of adjuvant KEYTRUDA IV infusion plus five cycles of enfortumab vedotin IV infusion, or;
Four cycles (each cycle is 21 days) of standard of care neoadjuvant chemotherapy followed by surgery.
The primary endpoint is EFS, defined as the time from randomization to the first occurrence of the following events: radiographic disease progression precluding radical cystectomy and pelvic lymph node dissection, failure to undergo surgery in participants with residual disease, gross residual disease left behind at time of surgery, local or distant recurrence based on blinded independent central review or death due to any cause. The key secondary endpoints are OS and pCR rate.
About bladder cancer
In 2022, bladder cancer changed the lives of more than 600,000 people around the world. According to some clinical practice guidelines, about 25% of newly diagnosed bladder cancer cases are MIBC. The standard of care for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery, which is shown to prolong survival. However, nearly half of patients who undergo this standard treatment experience recurrence.
(Press release, Merck & Co, DEC 17, 2025, View Source [SID1234661503])