FDA Gives Priority Review to PADCEV Plus Pembrolizumab in Broader Perioperative MI Bladder Cancer
20 April 2026
Key Takeaways
- The FDA has granted Priority Review to a supplemental application for perioperative enfortumab vedotin plus pembrolizumab in muscle-invasive bladder cancer, regardless of cisplatin eligibility.
- In the Phase 3 EV-304 trial, the regimen reduced the risk of recurrence, progression, or death by 47% and the risk of death by 35%, while increasing pathological complete response rates to 55.8% versus 32.5%.
The U.S. Food and Drug Administration has accepted for Priority Review a supplemental biologics license application seeking to expand the perioperative use of enfortumab vedotin-ejfv, PADCEV, plus pembrolizumab for patients with muscle-invasive bladder cancer, MIBC, regardless of cisplatin eligibility. The combination is already approved in the United States as perioperative therapy for cisplatin-ineligible MIBC, and the new filing aims to extend that indication to the broader MIBC population.
The FDA has set a target action date of August 17, 2026. If approved, the regimen could become the first perioperative option for MIBC that spans both cisplatin-eligible and cisplatin-ineligible patients, a clinically relevant distinction in a disease where relapse remains common even after curative-intent surgery.
The application is supported by results from the Phase 3 EV-304 trial, also known as KEYNOTE-B15, which compared perioperative enfortumab vedotin plus pembrolizumab with standard neoadjuvant gemcitabine and cisplatin in patients eligible for cisplatin-based chemotherapy. According to the companies, the combination reduced the risk of recurrence, progression, or death by 47% and reduced the risk of death by 35% versus standard chemotherapy. At surgery, the pathological complete response rate was 55.8% with the antibody-drug conjugate and immunotherapy combination, compared with 32.5% in the chemotherapy arm.
“For people with muscle‑invasive bladder cancer, surgery is often just the beginning of a long and uncertain journey, with far too many patients seeing their cancer return,” said Jeff Legos, PhD, MBA, Chief Oncology Officer, Pfizer. “If approved, perioperative PADCEV plus pembrolizumab could meaningfully change that experience, potentially helping patients reduce the risk of recurrence and live longer, regardless of whether they are eligible for cisplatin.”
Phase 3 EV-304 Trial
EV-304 is an ongoing, open-label, randomized Phase 3 study evaluating perioperative enfortumab vedotin plus pembrolizumab versus neoadjuvant gemcitabine and cisplatin in cisplatin-eligible patients with MIBC undergoing curative-intent cystectomy.
Patients assigned to the experimental arm received neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab, while the control arm received neoadjuvant gemcitabine and cisplatin before surgery. The study’s primary endpoint is event-free survival, with overall survival and pathological complete response among the key secondary endpoints.
The safety profile reported in EV-304 was consistent with prior experience for the combination, and no new safety signals were identified.
Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas said: “The data from the EV-304 trial take us another step closer to bringing perioperative enfortumab vedotin plus pembrolizumab to patients with muscle-invasive bladder cancer regardless of cisplatin eligibility, who still face a recurrence rate of more than fifty percent despite curative-intent surgery, highlighting the ongoing need for improved treatment strategies.”
About PADCEVTM (enfortumab vedotin-ejfv)
PADCEVTM (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death. PADCEV plus pembrolizumab is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) in the United States, the European Union, Japan and a number of other countries around the world. PADCEV is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.
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