Written By: Pharmacally Medical News Desk
The U.S. Food and Drug Administration on 21 November 2025 has granted approval for KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (a formulation of pembrolizumab combined with berahyaluronidase alfa-pmph), each used in combination with Padcev® (enfortumab vedotin-ejfv), as perioperative treatments for adult patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy. This approval marks a significant advancement in care options for this patient population that historically had limited effective therapies.
The approval is based on the results from the pivotal Phase 3 EV-303 (KEYNOTE-905) (ClinicalTrials.gov-NCT03924895) clinical trial, which showed that the combination of KEYTRUDA or KEYTRUDA QLEX with Padcev as neoadjuvant therapy before radical cystectomy and continued as adjuvant therapy afterward significantly improved event-free survival (EFS) and overall survival (OS) compared to surgery alone. Notably, KEYTRUDA plus Padcev demonstrated a 50% improvement in overall survival versus surgery alone, along with a 60% reduction in the risk of cancer recurrence or death. The trial enrolled patients who were either ineligible for or had declined cisplatin-based chemotherapy.
KEYTRUDA and KEYTRUDA QLEX are immune checkpoint inhibitors targeting PD-1 and have been used across several cancer types. Padcev is an antibody-drug conjugate targeting Nectin-4, a protein highly expressed in urothelial cancer cells. The combination harnesses immunotherapy and targeted cytotoxicity to attack tumor cells perioperatively, aiming to reduce recurrence risk after surgery. KEYTRUDA QLEX includes berahyaluronidase alfa-pmph, which facilitates subcutaneous administration and may enhance drug delivery.
The safety profile of these therapies includes risks of infusion- or administration-related reactions such as hypersensitivity and immune-mediated adverse events including colitis. Careful monitoring during treatment is recommended. Common adverse events observed included pneumonitis and rash, with permanent discontinuation rates due to side effects reported in a minority of patients. Surgical delays due to treatment-related adverse reactions were infrequent.
Dr. Matthew Galsky, Director of Genitourinary Medical Oncology at Mount Sinai Tisch Cancer Center, said pembrolizumab plus enfortumab vedotin addresses a critical unmet need as half of muscle-invasive bladder cancer patients face recurrence after bladder removal and many cannot receive cisplatin; this approval offers a practice-changing advance with significant survival benefits.
Dr. Marjorie Green, Senior VP and Head of Oncology at Merck, highlighted the company’s commitment to patient-centered innovation, emphasizing the new options provide these patients, who previously had only surgery, a choice of immunotherapy delivery via intravenous or subcutaneous administration.
This FDA approval provides a new perioperative treatment option that addresses the unmet need in MIBC patients who cannot tolerate cisplatin chemotherapy, offering a promising path to improved outcomes through a combination of immuno-oncology and targeted therapy.
References
FDA Approves KEYTRUDA® (pembrolizumab) and KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph), Each with Padcev® (enfortumab vedotin-ejfv), as Perioperative Treatment for Adults with Cisplatin-Ineligible Muscle-Invasive Bladder Cancer, 21 November 2025, MERCK, https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-and-keytruda-qlex-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-with-padcev-enfortumab-vedotin-ejfv-as-perioperative-treatment-for/
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 ID NCT03924895, https://clinicaltrials.gov/study/NCT03924895
Andrea Necchi et al, Phase 3 KEYNOTE-905/EV-303: Perioperative pembrolizumab (pembro) or pembro + enfortumab vedotin (EV) for muscle-invasive bladder cancer (MIBC) J Clin Oncol 41, TPS585-TPS585(2023), DOI:10.1200/JCO.2023.41.6_suppl.TPS585