FDA Approves Enfortumab Vedotin Plus Pembrolizumab for MIBC

The FDA has approved enfortumab vedotin (Padcev) plus pembrolizumab (Keytruda) for the treatment of patients with muscle-invasive bladder cancer (MIBC).¹

In October 2025, the FDA granted priority review to the supplemental biologics license application (sBLA) to the drug combination as a neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment.²

The FDA decision was based on the results of the phase 3 EV-303 (Keynote-905; NCT03924895)³ clinical trial. Enfortumab plus pembrolizumab reduced the risk of recurrence, progression, or death by 60% and the risk of death by 50% compared with surgery alone. Results of the trial were announced at the 2025 European Society of Medical Oncology (ESMO) Congress on October 18 in Berlin, Germany.

The EV-303 trial resulted in significantly improved event-free survival (HR, 0.40; 95% CI, 0.28-0.57; P <.0001) and overall survival (HR, 0.50; 95% CI, 0.33-0.74; P <.0002) when used before and after surgery in patients with MIBC who were ineligible for or declined cisplatin-based chemotherapy.²

Patients were randomized to 1 of 3 arms: neoadjuvant and adjuvant pembrolizumab, surgery alone, or neoadjuvant and adjuvant enfortumab vedotin in combination with pembrolizumab.

Those in the neoadjuvant and adjuvant pembrolizumab arm received 200 mg of pembrolizumab every 3 weeks and radical cystectomy plus pelvic lymph node dissection. Patients in the surgery alone arm received standard-of-care surgery. Patients in the neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab arm received 1.25 mg of enfortumab vedotin on days 1 and 8 of the 3-week cycle.

REFERENCES

1.FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. November 21, 2025. Accessed November 21, 2025. https://tinyurl.com/3t7bdzz2

2.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. Published October 21, 2025. Accessed October 31, 2025. https://tinyurl.com/bp6yfcnf

3.Perioperative pembrolizumab (MK-3475) plus cystectomy or perioperative pembrolizumab plus enfortumab vedotin plus cystectomy versus cystectomy alone in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MK-3475-905/KEYNOTE-905/EV-303). ClinicalTrials.gov. Updated August 28, 2025. Accessed November 18, 2025. https://clinicaltrials.gov/study/NCT03924895