On December 17, 2025, Merck & Co., Inc. (NYSE: MRK), known as MSD outside the United States and Canada, released promising topline results from its Phase 3 KEYNOTE-B15 trial (also referred to as EV-304). The trial evaluated the effectiveness of KEYTRUDA® (pembrolizumab) in combination with Padcev® (enfortumab vedotin-ejfv) in treating patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. The results indicate that this combination therapy significantly enhances event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rates compared to traditional neoadjuvant chemotherapy followed by surgery.

2. Clinical Significance of Results

Dr. Matthew Galsky, the principal investigator of the KEYNOTE-B15 study and director of genitourinary medical oncology at Mount Sinai Tisch Cancer Center, emphasized the importance of these findings. He noted the persistent risk of recurrence in patients with MIBC who are eligible for cisplatin-based chemotherapy, despite recent advancements in treatment. "The strength of these data demonstrates that pembrolizumab plus enfortumab vedotin—given before and after surgery—has the potential to significantly improve survival outcomes," Dr. Galsky stated.

The trial evaluated the combination therapy as both a neoadjuvant and adjuvant treatment, marking a significant step forward in the treatment landscape for bladder cancer.

3. Details of the KEYNOTE-B15 Trial

Conducted in collaboration with Pfizer and Astellas, the KEYNOTE-B15 trial enrolled 808 patients who were randomized to receive either:

Four cycles of neoadjuvant KEYTRUDA plus Padcev followed by surgery and then 13 cycles of adjuvant KEYTRUDA plus five cycles of Padcev; or

Four cycles of standard neoadjuvant chemotherapy (gemcitabine plus cisplatin) followed by surgery.

The primary endpoint of the study was EFS, defined as the time from randomization to the first occurrence of disease progression, failure to undergo surgery, or death. Key secondary endpoints included OS and pCR rates.

4. Safety Profile and Future Plans

The safety profile of the combination therapy was consistent with the known safety profiles of each agent, with no new safety signals identified during the study. Both Merck and its collaborators plan to share these results with regulatory authorities worldwide, anticipating future regulatory filings. The data will also be presented at an upcoming medical meeting.

Currently, KEYTRUDA plus Padcev is approved for adult patients with locally advanced or metastatic urothelial cancer in the U.S., European Union, Japan, and many other countries. It is also approved for MIBC patients who are ineligible for cisplatin-based chemotherapy.

5. A Broader Commitment to Cancer Treatment

Merck's commitment to advancing cancer treatment extends beyond this trial. The company is currently conducting three additional Phase 3 studies evaluating KEYTRUDA across all stages of bladder cancer, including non-muscle-invasive and metastatic forms. This includes trials such as KEYNOTE-866 and KEYNOTE-992 for MIBC, and KEYNOTE-676 for patients with non-muscle-invasive bladder cancer.

Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories, highlighted the importance of early intervention in cancer treatment. "These results reinforce our conviction that moving KEYTRUDA into earlier stages of cancer care can make a meaningful difference for patients," she stated.

6. Conclusion

The findings from the KEYNOTE-B15 trial represent a significant milestone in the treatment of muscle-invasive bladder cancer. With the potential for improved survival outcomes and a robust safety profile, Merck's innovative approach may redefine treatment protocols and provide hope for patients battling this challenging disease. As the company prepares to share these findings with regulatory authorities and the broader medical community, the focus on advancing cancer care remains a top priority for Merck.

Original press release