Keytruda Expands Approvals in Bladder and Ovarian Cancer in Canada, Korea and EU

Merck & Co., known as MSD outside the United States and Canada, has received new regulatory approvals for its anti-PD-1 therapy Keytruda (pembrolizumab) in Canada and South Korea, along with a positive European Medicines Agency recommendation, expanding its use in muscle-invasive bladder cancer and adding a new ovarian cancer indication in Korea.

Health Canada approved Keytruda in combination with enfortumab vedotin for certain adults with muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapy. The regimen is used as neoadjuvant treatment, followed by radical cystectomy, and then continued as adjuvant treatment after surgery. Enfortumab vedotin is an antibody-drug conjugate. The approval was based on data from the Phase 3 KEYNOTE-905 trial, also known as EV-303, conducted with Pfizer Inc. and Astellas Pharma Inc. The trial showed a statistically significant improvement in event-free survival and overall survival for patients treated with the combination versus radical cystectomy and pelvic lymph node dissection alone, and a statistically significant difference in pathological complete response rate. "Muscle-invasive bladder cancer can have a significant impact on patients and their families, particularly for those who are not candidates for cisplatin-based chemotherapy," said the Executive Director at Bladder Cancer Canada.

In South Korea, the Ministry of Food and Drug Safety approved Keytruda for use in combination with enfortumab vedotin as neoadjuvant and adjuvant therapy around radical cystectomy for patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy. In the KEYNOTE-905 trial, the combination reduced the risk of disease progression or other disease-related events by 60 percent compared with the control group (HR=0.40), lowered the risk of death by 50 percent (HR=0.50), and demonstrated a statistically significant improvement in pathological complete response, with a 48.3 percentage-point advantage over the control arm. Bladder cancer primarily affects older adults, particularly those aged 70 years and older, and many patients cannot receive standard cisplatin-based chemotherapy because of advanced age or impaired kidney function.

Keytruda also received approval in Korea in combination with paclitaxel, with or without bevacizumab, for patients with PD-L1-positive (CPS ≥1), platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have previously received one or two lines of systemic therapy. In the Phase 3 KEYNOTE-B96 trial involving 643 patients with recurrent disease, the Keytruda-based combination reduced the risk of disease progression or death by 28 percent compared with the control group (HR=0.72), reduced the risk of death by 24 percent in the overall survival analysis (HR=0.76), and achieved a median overall survival of 18.2 months. Ovarian cancer has a recurrence rate of approximately 70 percent to 80 percent. With the latest approvals, Keytruda now holds 37 approved indications across 18 cancer types in Korea. "The expanded indications are particularly meaningful because they offer new hope to patients with platinum-resistant ovarian cancer and muscle-invasive bladder cancer, where treatment options have been limited," said an Executive Director of the Oncology Business Division at MSD Korea.

Separately, the European Medicines Agency's Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of Merck's Keytruda-Padcev combination as perioperative treatment, given before and after surgery, in adults with resectable muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapy. The recommendation is based on the Phase 3 KEYNOTE-905 trial, which showed improvements to survival rates. The combination is already approved in the U.S. The recommendation will now be reviewed by the European Commission for marketing authorization in the EU, Iceland, Liechtenstein and Norway, with a final decision expected in the third quarter of this year.

Health Canada also approved Keytruda SC, a subcutaneous formulation of pembrolizumab, offering an alternative to the current intravenous infusion. The decision was based on results from pivotal trial 3475A-D77, in which the subcutaneous formulation delivered similar drug levels and effectiveness as the IV version when used with chemotherapy in certain lung-cancer patients. Merck said its rollout in Canada will depend on provincial and territorial reimbursement decisions.