FDA grants priority review to sBLA for EV plus pembrolizumab in cisplatin-ineligible MIBC

The FDA has granted priority review to 2 supplemental biologics license applications for pembrolizumab (Keytruda) and pembrolizumab and berahyaluronidase alfa-pmph (Keytruda QLEX), each in combination with enfortumab vedotin-ejfv (Padcev), as perioperative regimens for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy, Astellas and Merck announced in separate news releases.^1,2

The PDUFA target action date is set for April 7, 2026.

The application is supported by results from the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895), which were recently presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.³ Data from the trial showed that a treatment regimen consisting of neoadjuvant EV plus pembrolizumab, radical cystectomy plus pelvic lymph node dissection, and adjuvant EV plus pembrolizumab yielded significant improvements in event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rate compared with surgery alone.

The 3-arm, open-label trial randomly assigned patients to either neoadjuvant and adjuvant pembrolizumab (arm A), surgery alone (arm B) or neoadjuvant and adjuvant EV plus pembrolizumab (arm C). The primary end point was EFS between arm B and C, as assessed by blinded independent central review. Key secondary end points included OS, pCR, and safety.

Overall, the study met its primary end point, showing that perioperative EV plus pembrolizumab reduced the risk of recurrence, progression, or death by 60% compared with surgery alone. The median EFS was not reached (95% CI, 37.3 to NR) in the EV plus pembrolizumab arm vs 15.7 months (95% CI, 10.3 to 20.5) in the control arm (HR, 0.40; 95% CI, 0.28 to 0.57, one-sided P < .0001). The EFS benefits were observed across subgroups in the study.

Further, the perioperative regimen reduced the risk of death by 50% compared with surgery alone. The median OS was not reached in the EV plus pembrolizumab group vs 41.7 months in the control group (HR, 0.50; 95% CI, 0.33 to 0.74, one-sided P = .0002).

“This is the first trial to show an overall survival benefit in this population,” presenting author Christof Vulsteke, MD, PhD, noted during the presentation at ESMO. Like EFS, the OS gains were observed across patient subgroups.

Ninety-seven patients in the EV plus pembrolizumab group achieved a pCR vs 15 patients in the control group. The pCR rate was 57.1% (95% CI, 49.3 to 64.6) in the EV plus pembrolizumab group vs 8.6% (95% CI, 4.9 to 13.8) in the control group.

For patients receiving EV plus pembrolizumab who had a pCR, median EFS was NR (95% CI, NR to NR) vs 41.2 months (95% CI, 12.7 to NR) in the control arm (HR, 0.43; 95% CI, 0.16 to 0.16). For patients receiving EV plus pembrolizumab who did not have a pCR, median EFS was 26.1 months (95% CI, 10.1 to 41.2) vs 14.2 months in the control arm (95% CI, 10.1 to 19.5).

Regarding safety, any-grade treatment-emergent adverse events (TEAEs) were reported in 167 (100%) patients in the EV plus pembrolizumab group vs 103 (64.8%) patients in the control group. Grade 3 or higher TEAEs were seen in 119 (71.3%) patients in the EV plus pembrolizumab group vs 73 (45.9%) patients in the control group.

TEAEs leading to dose reduction of EV occurred in 28 (16.8%) patients and TEAEs leading to discontinuation of EV occurred in 69 (41.3%) patients. TEAEs leading to discontinuation of pembrolizumab occurred in 57 (34.1%) patients and TEAEs leading to death occurred in 13 (7.8%) patients in the EV plus pembrolizumab arm vs 9 (5.7%) patients in the control arm.

“KEYNOTE-905 is the first phase 3 trial to show an improved efficacy outcome with peri-op therapy relative to surgery for patients with MIBC who are ineligible for cisplatin-based chemotherapy,” Vulsteke concluded during the presentation at ESMO. “Perioperative enfortumab vedotin and pembrolizumab added to surgery may represent a new standard of care in this population with a high unmet medical need.”

REFERENCES

1. PADCEV™ (enfortumab vedotin-ejfv) Plus KEYTRUDA® (pembrolizumab) sBLA Granted FDA Priority Review for Treatment of Certain Patients with Muscle-Invasive Bladder Cancer. News release. Astellas Pharma, Inc. October 22, 2025. Accessed October 22, 2025. https://newsroom.astellas.com/2025-10-21-PADCEV-TM-enfortumab-vedotin-ejfv-Plus-KEYTRUDA-R-pembrolizumab-sBLA-Granted-FDA-Priority-Review-for-Treatment-of-Certain-Patients-with-Muscle-Invasive-Bladder-Cancer

2. FDA Grants Priority Review for KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph), Each in Combination with Padcev® (enfortumab vedotin-ejfv), for Certain Patients with Muscle-Invasive Bladder Cancer. News release. Merck. October 23, 2025. Accessed October 23, 2025. https://www.merck.com/news/fda-grants-priority-review-for-keytruda-pembrolizumab-and-keytruda-qlex-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-in-combination-with-padcev-enfortumab-vedotin-ejfv/

3. Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible: The phase III KEYNOTE-905 study. Presented at: 2025 European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract LBA2. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA2.html.pdf