US pharma giant Merck has reported positive topline results from a pivotal Phase 3 trial showing that a combination of KEYTRUDA and Padcev significantly improved survival outcomes for patients with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy.

 

The KEYNOTE-B15 trial met its primary and key secondary endpoints, demonstrating statistically significant and clinically meaningful improvements in event-free survival, overall survival and pathologic complete response rates compared with standard neoadjuvant chemotherapy followed by 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,” said Matthew Galsky, principal investigator of the study. “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 study evaluated KEYTRUDA, Merck’s anti-PD-1 immunotherapy, in combination with Padcev, an antibody-drug conjugate developed with partners Pfizer and Astellas. The regimen was given both before and after surgery, targeting patients earlier in the course of disease. The results build on the combination’s prior success in locally advanced or metastatic urothelial cancer and in cisplatin-ineligible muscle-invasive disease.

 

“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 Marjorie Green, senior vice president and head of oncology, global clinical development at 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.”

 

Merck said the safety profile of the combination was consistent with the known profiles of each drug, with no new safety signals identified. The company plans to submit the data to regulators worldwide and present the findings at an upcoming medical meeting.

 

KEYTRUDA plus Padcev is already approved in the US, European Union, Japan and other regions for adults with locally advanced or metastatic urothelial cancer, and in the U.S. for certain patients with muscle-invasive bladder cancer who are ineligible for cisplatin. Merck is also running multiple late-stage trials evaluating KEYTRUDA across all stages of bladder cancer, including additional Phase 3 studies in muscle-invasive and non-muscle-invasive disease.

 

Bladder cancer remains a significant global burden, affecting more than 600,000 people worldwide in 2022.