Merck has announced that the US Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) in combination with Padcev (enfortumab vedotin-ejfv) as perioperative treatment for adults with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy.
The approvals represent the first PD-1 inhibitor plus ADC regimens for this patient population. Treatment involves Keytruda or Keytruda Qlex with Padcev before surgery and continued after cystectomy.
The decision is based on results from the phase 3 Keynote-905 trial, also known as EV-303, conducted with Pfizer and Astellas.
After a median follow-up of 25.6 months, the combination showed a 60% reduction in the risk of event-free survival events compared with surgery alone. Overall survival improved by 50%, while pathologic complete response rates were significantly higher at 57.1% versus 8.6%.
Keytruda Qlex is contraindicated in patients with hypersensitivity to berahyaluronidase alfa, hyaluronidase or its excipients. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system. Both treatments can also cause infusion-related reactions and may result in fetal harm if administered during pregnancy.
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, explained: “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.”
