Key takeaways:
- Merck’s FDA clearance introduces the first PD-1 inhibitor and ADC combination for cisplatin-ineligible MIBC patients, widening its position in the bladder cancer treatment space.
- Strong Keynote-905 results may shift perioperative management by elevating the Keytruda–Padcev regimen as a viable alternative to surgery alone.
- Intravenous and subcutaneous delivery options give providers more flexibility, which could support broader clinical uptake.
Merck said the US Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) for use alongside Padcev (enfortumab vedotin-ejfv) as a perioperative regimen for adults with muscle-invasive bladder cancer (MIBC) who cannot receive cisplatin-based chemotherapy.
Under the newly approved approach, patients are treated with Keytruda or Keytruda Qlex combined with Padcev prior to surgery, with therapy resuming after cystectomy. The decision marks the first time a PD-1 inhibitor and antibody-drug conjugate combination has been authorised for this specific patient group.
Regulators issued the approval after reviewing findings from the phase 3 Keynote-905 study, also known as EV-303, which Merck conducted in collaboration with Pfizer and Astellas. In the trial, researchers reported that after a median follow-up of 25.6 months, the combined therapy reduced the risk of event-free survival events by 60% when compared with surgery alone. Investigators also observed a 50% improvement in overall survival, while the pathologic complete response rate reached 57.1% versus 8.6% in the control arm.
The company noted that Keytruda Qlex carries a contraindication for patients with hypersensitivity to berahyaluronidase alfa, hyaluronidase or any of the formulation’s excipients. Merck also highlighted that immune-mediated reactions, potentially severe or fatal, may arise across organ systems. Infusion-related events remain a known risk for both treatments, and the therapies can cause fetal harm if administered during pregnancy.
Commenting on the clinical relevance, Dr Matthew Galsky, Lillian and Howard Stratton Professor of Medicine at Mount Sinai Tisch Cancer Center and Keynote-905 investigator, said: “Pembrolizumab plus enfortumab vedotin is poised to address a critical unmet need. Half of patients with MIBC may experience cancer recurrence even after having their bladder removed, and many of these patients are ineligible to receive cisplatin.”
Dr Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, added: “We are honoured to provide these patients who previously had only one option — surgery — with a choice to receive their immunotherapy either intravenously or subcutaneously.”
