FDA grants priority review to EV plus pembrolizumab for cisplatin-eligible MIBC

The FDA has granted priority review to supplemental biologics license applications (sBLAs) for pembrolizumab (Keytruda) and pembrolizumab and berahyaluronidase alfa-pmph (KEYTRUDA QLEX), each in combination with enfortumab vedotin-ejfv (Padcev; EV), for the perioperative treatment of patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy, issuing a PDUFA target action date of August 17, 2026.^1,2

The applications are based on data from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124), presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium, which marked the first time in nearly 25 years that a nonplatinum-based regimen has surpassed cisplatin-based neoadjuvant chemotherapy in cisplatin-eligible MIBC.³

“Results from KEYNOTE-B15 challenge long-held expectations for patients with muscle-invasive bladder cancer,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories in a news release from Merck. “Even with curative-intent surgery and chemotherapy, patients still experience disease progression or limited survival. These data add to the growing body of evidence demonstrating that KEYTRUDA and KEYTRUDA QLEX, each in combination with Padcev, have the potential to reshape how we approach treatment for these patients and improve outcomes for people facing this aggressive disease.”¹

About KEYNOTE-B15/EV-304

The trial enrolled 808 patients who were randomly assigned 1:1 to receive perioperative EV plus pembrolizumab and radical cystectomy with pelvic lymph node dissection (n = 405), or to standard neoadjuvant gemcitabine plus cisplatin (n = 403) followed by surgery. The experimental arm received 4 neoadjuvant cycles of EV plus pembrolizumab, followed by 5 adjuvant cycles of EV and 13 adjuvant cycles of pembrolizumab; the control arm underwent observation after surgery.³

The trial met its primary end point of event-free survival (EFS). Median EFS was not reached in the EV/pembrolizumab arm vs 48.5 months in the gemcitabine/cisplatin arm. At 2 years, the estimated EFS rate was 79.4% with EV/pembrolizumab vs 66.2% in the control arm (HR, 0.53; 95% CI, 0.41 to 0.70; P < .0001). Overall survival (OS) was also significantly improved, with a 35% reduction in the risk of death (HR, 0.65; 95% CI, 0.48 to 0.89; P = .0029) and a 24-month estimated OS rate of 86.9% in the EV/pembrolizumab arm vs 81.3% in the control arm.³

The pathologic complete response (pCR) rate at surgery was 55.8% with EV/pembrolizumab vs 32.5% with gemcitabine/cisplatin—a difference of 23.4 percentage points (P < .0001). Among patients who underwent cystectomy, the pCR rate in the EV/pembrolizumab arm reached 64.4%.³

Presenting investigator Matthew D. Galsky, MD, of the Icahn School of Medicine at Mount Sinai, framed the significance of the findings in historical context.

"For the first time since cisplatin-based neoadjuvant therapy was shown to improve outcomes in patients with muscle-invasive bladder cancer, almost 25 years ago, a nonplatinum-based regimen has surpassed it," he said.³ The EFS benefit was consistent across subgroups stratified by age, sex, race, region, PD-L1 combined positive score, and tumor stage.

Related: The UroOnc Minute: KEYNOTE-B15 and Perioperative Therapy in MIBC

Grade 3 or higher treatment-emergent adverse events occurred in 75.7% of patients in the EV/pembrolizumab arm vs 67.2% in the gemcitabine/cisplatin arm, with 2 treatment-related deaths in the experimental arm and 1 in the control arm. The safety profile was consistent with prior experience with the combination, and no new signals were identified.³

Significance of potential new indications

If approved, the new indications would extend the perioperative use of EV plus pembrolizumab—or its subcutaneous formulation pembrolizumab and berahyaluronidase alfa-pmph— to cisplatin-eligible patients, building on the November 2025 approval of the combination for cisplatin-ineligible MIBC.^1,2 Combined with results from KEYNOTE-905, which demonstrated benefit in cisplatin-ineligible patients,⁴ the data support a regimen that may ultimately apply regardless of cisplatin eligibility status.

"The results of these 2 independent phase 3 studies reinforce both the reproducibility and generalizability of outcomes with this treatment regimen," Galsky said.³

Added Moitreyee Chatterjee-Kishore, PhD, MBA, head of Oncology Development at Astellas Pharma, "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 50% despite curative-intent surgery, highlighting the ongoing need for improved treatment strategies."²

REFERENCES

1. FDA grants priority review for KEYTRUDA and KEYTRUDA QLEX, each with Padcev, for cisplatin-eligible patients with muscle-invasive bladder cancer. News release. Merck. April 20 2026. Accessed 20, 2026. https://www.businesswire.com/news/home/20260420766130/en/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
2. Astellas Pharma/Pfizer. U.S. FDA grants priority review to sBLA for Padcev + Keytruda as perioperative treatment for muscle-invasive bladder cancer regardless of cisplatin eligibility. News release. Astellas Pharma. April 20 2026. Accessed April 20, 2026. https://www.prnewswire.com/news-releases/us-fda-grants-priority-review-to-sbla-for-padcev--keytruda-as-perioperative-treatment-for-muscle-invasive-bladder-cancer-regardless-of-cisplatin-eligibility-302746360.html
3. Galsky MD, Pérez-Valderrama B, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab for participants with muscle-invasive bladder cancer who are eligible for cisplatin: randomized, open-label, phase 3 KEYNOTE-B15 study. Abstract LBA630. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 26–28, 2026; San Francisco, CA
4. Vulsteke C, Adra N, Danchaivijitr P, et al. Perioperative enfortumab vedotin and pembrolizumab in bladder cancer. N Engl J Med. 2026;394(13):1257-1269. doi:10.1056/NEJMoa2511674