FDA Grants Priority Review to Enfortumab/Pembrolizumab in Perioperative MIBC

The FDA has granted a priority review to the supplemental Biologics License Application (sBLA) to the combination of enfortumab vedotin-ejfv (EV; Padcev) and pembrolizumab and berahyaluronidase alfa-pmph (Keytruda QLEX) in the perioperative setting in cisplatin-eligible or -ineligible patients with muscle-invasive bladder cancer (MIBC).¹ The filing expands the cisplatin-ineligible indication to include all patients with MIBC.

Priority review is granted to agents that may offer significant advances in treatment or may provide a treatment where limited therapy options exist. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of August 17, 2026.

“The data from the EV-304 trial [NCT04700124] 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,” Moitreyee Chatterjee-Kishore, PhD, MBA, head of oncology development, Astellas, said in a release.

The submission was based on findings from the phase 3 EV-304/KEYNOTE-B15 trial that were presented during the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.²

In the trial, event-free survival (EFS) was significantly longer in patients who received EV/pembrolizumab than in those who received cisplatin and gemcitabine. The median EFS was not reached in the EV/pembrolizumab arm vs 48.5 months for the cisplatin/gemcitabine arm. At 24 months, the EFS rate was 79.4% for EV/pembrolizumab vs 66.2% for cisplatin/gemcitabine (HR, 0.53; 95% CI, 0.41-0.70); P < .001).²

The secondary end point of median overall survival was not reached in the control or treatment arms. The combination also demonstrated a pathological complete response (pCR) rate of 55.8% compared with 32.5% pCR rate in the chemotherapy arm at the time of surgery.¹

Background on EV-304/KEYNOTE-B15

EV-304/KEYNOTE-B15 enrolled patients with clinically localized, muscle-invasive urothelial cancer of the bladder who were eligible for cisplatin-based chemotherapy and radical cystectomy. A total of 808 patients were randomly assigned 1:1 between May 2021 and December 2023.

The study compared 1.25 mg/kg of EV plus pembrolizumab (n = 405) vs 70 mg/m² of cisplatin and 1000 mg/m² of gemcitabine (n = 403). Patients underwent 4 cycles for each arm, followed by radical cystectomy. Patients assigned to the EV/pembrolizumab arm initially received EV for 5 cycles and pembrolizumab for 13 cycles. Patients in the control arm were observed following cystectomy.

The safety profile for the combination was consistent with prior experience and no new safety signals were reported. These data will be discussed with additional global health authorities for potential regulatory filings.

“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. If approved, perioperative [EV] 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,” Jeff Legos, PhD, MBA, chief oncology officer, Pfizer, said in a release.

What is Enfortumab Vedotin?

EV 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.³ EV 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.

REFERENCES

1. US FDA grants priority review to sBLA for Padcev + Keytruda as perioperative treatment for muscle-invasive bladder cancer regardless of cisplatin eligibility. News release. Pfizer. April 20, 2026. Accessed April 20, 2026. https://tinyurl.com/u9bn8nwc

2. 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

3. Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 2016;76(10):3003-13.