FDA OKs Pembrolizumab/Enfortumab Vedotin in Muscle Invasive Bladder Cancer

The FDA has approved neoadjuvant followed by adjuvant treatment after cystectomy consisting of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) plus enfortumab vedotin-ejfv (Padcev) for patients with muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin, according to a press release by the FDA.¹

The approval was based on the results from the phase 3 KEYNOTE-905/EV-303 (NCT03924895) assessing 344 patients with previously untreated MIBC who were candidates for radical cystectomy (RC), had pelvic lymph node dissection (PLND), and were ineligible for or had declined cisplatin-based chemotherapy.

The median event-free survival was not reached (NR; 95% CI, 37.3-NR) in the combination arm vs 15.7 months (95% CI, 10.3-20.5) in the RC/PLND alone arm (HR, 0.40; 95% CI, 0.28-0.57; P <.0001). The median OS was NR (95% CI, NR-NR) in the combination arm and 41.7 months (95% CI, 31.8-NR) in the RC/PLND arm (HR, 0.50; 95% CI, 0.33-0.74; P = .0002).

The safety for the pembrolizumab combination in the trial was similar to what has been observed in previous trials with the combination.

For neoadjuvant pembrolizumab, the recommended dose is 200 mg intravenously every 3 weeks given in combination with enfortumab vedotin at 1.25 mg/kg intravenously on days 1 and 8 of a 21-day cycle for 3 cycles with a total duration of 9 weeks.

Adjuvant treatment consisted of enfortumab vedotin continuing for 6 additional cycles every 3 weeks plus pembrolizumab given at either 200 mg intravenously every 3 weeks for 14 cycles or 400 mg every 6 weeks for 7 cycles. The overall duration of adjuvant therapy was 42 weeks.

In October 2025, the FDA granted priority review to the combination, with an original Prescription Drug User Fee Act date of April 7, 2026.²

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/bdfhmhnk
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. October 21, 2025. Accessed November 21, 2025. https://tinyurl.com/5n969kx4