Merck announced positive topline results from the phase III 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.

“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. The strength of these data demonstrates that pembrolizumab plus enfortumab vedotin—given before and after surgery—has the potential to significantly improve survival outcomes,” 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 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 the greatest. 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,” said Dr Marjorie Green, Senior Vice President and Head, Oncology, Global Clinical Development, Merck Research Laboratories.

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 US, the European Union (EU), Japan and several other countries around the world. KEYTRUDA plus Padcev is also approved in the US for the treatment of adult patients with MIBC who are ineligible for cisplatin-based chemotherapy. KEYTRUDA as monotherapy is also approved in the US, EU, Japan and other countries for the treatment of certain patients with la/mUC or a type of 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).