Regulatory Decision Summary for Keytruda
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Product type:
Contact:
Medicinal Ingredient(s):
Pembrolizumab
Control Number:
274453
Brand/Product Name:
Keytruda
Therapeutic Area:
Antineoplastic Agents
Type of Submission:
Supplement to a New Drug Submission
Decision Issued:
Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations
What was the purpose of this submission?
The purpose of this Supplemental New Drug Submission was to seek market authorization for Keytruda (pembrolizumab), for the treatment of adult patients with resectable non-small cell lung cancer (NSCLC).
After evaluation of the totality of evidence submitted, Health Canada has authorized Keytruda for use for the treatment of adult patients with resectable Stage II, IIIA, or IIIB (T3-4N2) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery.
Why was the decision issued?
Authorization was based on the results of the Keynote-671 study, a Phase 3, randomized, double-blind, placebo-controlled trial investigating the use of pembrolizumab in combination with platinum-based chemotherapy as a neoadjuvant treatment followed by pembrolizumab monotherapy as an adjuvant treatment after surgery in patient with resectable Stage II, IIIA, or IIIB (T3-4N2) NSCLC. The study was designed with dual primary endpoints of event-free survival (EFS) and overall survival (OS).
In Keynote-671, 797 patients were randomized (1:1) to receive, pembrolizumab (pembrolizumab arm) or placebo (placebo arm), in combination with platinum-based chemotherapy (neoadjuvant treatment), followed after surgery by treatment with pembrolizumab or placebo alone (adjuvant treatment). In the neoadjuvant setting pembrolizumab was administered intravenously at a dose of 200 mg every 3 weeks for 4 cycles (21 days/cycle) in combination with chemotherapy. In the adjuvant setting, pembrolizumab alone was administered intravenously at a dose of 200 mg every 3 weeks for 13 cycles (21 days/cycle). The study demonstrated statistically significant and clinically meaningful improvements in EFS and OS in patients who received pembrolizumab in combination with platinum-based chemotherapy as a neoadjuvant treatment followed by pembrolizumab monotherapy as an adjuvant treatment after surgery. The median EFS was not reached for patients in the pembrolizumab arm and 17.0 months for patients in the placebo arm. The hazard ratio was 0.58, representing a 42% reduction in the risk of an event for patients in the pembrolizumab arm. The median OS was not reached for patients in the pembrolizumab arm and 52.4 months for patients in the placebo arm. The hazard was 0.72, representing a 28% reduction in the risk of death for patients in the pembrolizumab arm.
The adverse event (AE) profile observed in patients treated with pembrolizumab in combination platinum-based chemotherapy in the neoadjuvant setting followed by pembrolizumab as a single agent after surgery was consistent with the established safety profile pembrolizumab and as expected with its use in combination with chemotherapy. The most common treatment-related adverse events (reported in at least 20% of patients) were nausea, neutrophil count decreased, anemia, white blood cell count decreased, fatigue, constipation, and decreased appetite. Known risks included hypothyroidism, hyperthyroidism, pneumonitis, severe skin reactions, colitis, and thyroiditis was observed with a higher incidence in patients treated with pembrolizumab. A higher percentage of patients in the pembrolizumab arm compared to the placebo arm had serious AEs (40.4% vs. 32.6%), discontinuation of any study drug due to an AE (25.5% vs. 17.3%), discontinuation of pembrolizumab or placebo due to an AE (21.0% vs. 9.0%). No new safety signals were identified. The risks with this treatment regimen, and appropriate risk management strategies, have been adequately described in the Product Monograph.
Overall, the benefit-risk is positive for the recommended indication. The safety profile is considered acceptable in the context of the prognosis of the patient population and when used according to the instructions in the Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.
The recommended dosing regimen of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks. For the neoadjuvant and adjuvant treatment of resectable NSCLC, patients should be treated with 4 doses of 200 mg or 2 doses of 400 mg of neoadjuvant Keytruda in combination with chemotherapy or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with Keytruda as monotherapy for 13 doses of 200 mg or 7 doses of 400 mg or until disease recurrence or unacceptable toxicity.
An updated Risk Management Plan (RMP) for Keytruda was reviewed by Health Canada and considered acceptable.
Following review and requested revisions, the final labelling and Product Monograph were considered acceptable.
For further details about the recommended use of Keytruda (pembrolizumab), please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.
Date of Decision:
2025-02-06
Manufacturer/Sponsor:
Drug Identification Number(s) Issued:
N/A
Prescription Status:
Available by prescription only
Date Filed:
2023-04-17
Related Drug Products
Product name | DIN | Company name | Active ingredient(s) & strength |
---|---|---|---|
KEYTRUDA | 02456869 | MERCK CANADA INC | PEMBROLIZUMAB 25 MG / ML |