FDA OKs Pembrolizumab/EV Combo in Muscle Invasive Bladder Cancer

The FDA has approved pembrolizumab (Keytruda) with enfortumab vedotin-ejfv (Padcev) with or without berahyaluronidase alfa-pmph (Keytruda Qlex) for the neoadjuvant treatment of patients with muscle invasive bladder cancer (MIBC) followed by adjuvant treatment after cystectomy, according to a news release from the agency.¹ This approval extends the prior approval among cisplatin-ineligible patients who are candidates for cystectomy.²

Findings supporting the regulatory decision came from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124), which evaluated the regimen against cisplatin and gemcitabine in patients eligible for cisplatin-based therapy and radical cystectomy in a 1:1 ratio.³ Among 808 patients enrolled in the multicenter trial with previously untreated disease, the median EFS was not reached (NR; 95% CI, NR-NR) among those treated in the pembrolizumab-containing arm vs 48.5 months (95% CI, 43.3-NR) in the gemcitabine/cisplatin arm (HR, 0.53; 95% CI, 0.41-0.70; P <.0001). In addition, the median overall survival (OS) was NR in both arms, although the HR favored the investigational regimen (HR, 0.65; 95% CI, 0.48-0.89; P = .0029).

Regarding safety outcomes, the profile of the pembrolizumab/enfortumab vedotin regimen was similar to that observed in prior urothelial cancer trials evaluating this combination. Moreover, prescribing information for pembrolizumab lists warnings and precautions including immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity. For enfortumab vedotin, they included warnings and precautions for skin reactions, hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.

The recommended dose for pembrolizumab in the neoadjuvant setting is 200 mg of the intravenous formulation every 3 weeks or 400 mg given every 6 weeks. Intravenous enfortumab vedotin is recommended at 1.25 mg/kg up to a maximum of 125 mg for patients at 100 kg or greater on day 1 and 8 of each of the four 21-day cycles.

In the adjuvant setting, enfortumab vedotin should be continued for an additional 5 cycles every 3 weeks in combination with pembrolizumab at 200 mg for thirteen 3-week cycles or 400 mg for seven 6-week cycles.

References

1. FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. July 10, 2026. Accessed July 10, 2026. https://tinyurl.com/ywwuhr5k
2. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. November 21, 2025. Accessed July 10, 2026. https://tinyurl.com/bdfhmhnk
3. 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