The FDA is taking a closer, faster look at a new treatment approach for some people with muscle-invasive bladder cancer (MIBC) who can receive cisplatin chemotherapy. This approach combines two medicines—pembrolizumab (Keytruda), an immunotherapy, and enfortumab vedotin (Padcev), an antibody–drug conjugate—given before and after bladder removal surgery.
What did the FDA decide?
- The FDA has granted “priority review” to two applications asking to approve pembrolizumab (given by IV) or a newer under-the-skin version of pembrolizumab, each combined with enfortumab vedotin.
- These combinations are being reviewed for people with MIBC who are healthy enough to receive cisplatin-based chemotherapy.
- The FDA plans to make a decision by August 17, 2026.
- This would build on an earlier approval of the same drug combination for people with MIBC who cannot safely receive cisplatin, and for people with more advanced urothelial (bladder and urinary tract) cancers.
What is KEYNOTE-B15?
KEYNOTE-B15 (also called EV-304) is a large phase 3 clinical trial that compared this immunotherapy–antibody–drug combination with standard chemotherapy.
- The study enrolled adults with muscle-invasive bladder cancer who were candidates for bladder removal surgery and for cisplatin-based chemotherapy.
- Patients were randomly assigned to:
- Pembrolizumab plus enfortumab vedotin before surgery, followed by more of the same combination after surgery, or
- Standard chemotherapy (cisplatin plus gemcitabine) before surgery and then observation after surgery.
The main goal was to see how long patients lived without cancer events such as the cancer coming back, getting worse, or causing death (called event-free survival).
What have the results shown so far?
Early results suggest that the pembrolizumab plus enfortumab vedotin combination may help keep the cancer from coming back or progressing longer than standard chemotherapy.
- At the time of reporting, the median time before a cancer event happened had not yet been reached in the combination group, meaning many people were still doing well.
- In the chemotherapy group, the median event-free survival was about 4 years.
- The risk of a cancer event was reduced by about half with the combination compared with chemotherapy alone.
- More patients who received the combination had no signs of cancer left in the bladder or lymph nodes at the time of surgery (pathologic complete response).
Overall survival (how long patients live) is still being followed, but early data suggest a meaningful reduction in the risk of death with the combination compared with chemotherapy.
What about side effects?
As with many cancer treatments, side effects are common and can be serious.
- In KEYNOTE-B15, almost all patients in both groups had some treatment-related side effects.
- Serious and higher-grade side effects were somewhat more common in people who received the pembrolizumab plus enfortumab vedotin combination than in those who received chemotherapy.
- The types of side effects seen with the combination were generally similar to what has been reported in earlier studies of these drugs, including skin problems, nerve changes, fatigue, and changes in blood counts or organ function.
Because these medicines can affect the immune system and nerves, people taking them need close monitoring and prompt reporting of new symptoms.
What this could mean for patients
If the FDA approves these applications, pembrolizumab plus enfortumab vedotin could become a new option before and after surgery for people with muscle-invasive bladder cancer who are able to receive cisplatin. This would expand access to this combination so that it could be used for patients regardless of whether they are eligible for cisplatin, since it is already approved for those who cannot receive cisplatin and for people with more advanced disease.
If you have muscle-invasive bladder cancer, talk with your oncology team about current treatment options, including surgery, chemotherapy, immunotherapy, and clinical trials, and whether combinations like pembrolizumab plus enfortumab vedotin might be appropriate for you based on your overall health and cancer stage.
References:
FDA grants priority review for Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph), each with Padcev (enfortumab vedotin-ejfv), for cisplatin-eligible patients with muscle-invasive bladder cancer. News release. Merck. https://www.merck.com/news/fda-grants-priority-review-for-keytruda-pembrolizumab-and-keytruda-qlex-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-with-padcev-enfortumab-vedotin-ejfv-for-cisplati/
Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi: 10.1200/JCO.2026.44.7_suppl.LBA630
