FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer

FDA approval (July 10, 2026)

The FDA approved pembrolizumab (Keytruda) or pembrolizumab/berahyaluronidase alfa-pmph (Keytruda Qlex), each in combination with enfortumab vedotin-ejfv (Padcev), as neoadjuvant treatment followed by adjuvant treatment after cystectomy for adults with muscle invasive bladder cancer (MIBC) who are candidates for cystectomy. This extends a prior approval in this setting from cisplatin-ineligible patients to all cystectomy-eligible MIBC patients.

Supporting evidence

Efficacy and safety were evaluated in KEYNOTE-B15/EV-304 (NCT04700124), an open-label, randomized, active-controlled, multicenter trial (n=808) in previously untreated MIBC patients eligible for cisplatin-based chemotherapy and radical cystectomy with pelvic lymph node dissection.

Patients were randomized 1:1 to perioperative pembrolizumab + enfortumab vedotin vs neoadjuvant gemcitabine + cisplatin, both followed by surgery.

Primary endpoint: event-free survival (EFS) by blinded independent central review; overall survival (OS) was additional.

Results favored perioperative pembrolizumab + enfortumab vedotin: median EFS NR vs 48.5 months (HR 0.53; 95% CI 0.41–0.70; p<0.0001). Median OS NR in both arms (HR 0.65; 95% CI 0.48–0.89; p=0.0029).

Safety and dosing notes

Safety was reported as similar to prior urothelial cancer experience with this combination; labeling includes immune-mediated risks (pembrolizumab) and risks including skin reactions, hyperglycemia, pneumonitis/ILD, neuropathy, ocular disorders, and extravasation (enfortumab vedotin). Dosing details are provided in the prescribing information; pembrolizumab is administered after enfortumab vedotin when given on the same day.

Review occurred under Project Orbis; reviews at partner agencies were ongoing.