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:
Medicinal ingredient(s):
Therapeutic area:
Type of submission:
Control number:
What was the purpose of this submission?
The purpose for this Priority Review - Supplemental New Drug Submission was to review clinical efficacy and safety data available from a pivotal clinical trial for the use of Keytruda (pembrolizumab) in the treatment of unresectable or metastatic melanoma in patients who have not received prior treatment with ipilimumab.
Why was the decision issued?
The Phase III study KEYNOTE-006 demonstrated a statistically significant difference in the median progression free survival (PFS) favouring the combined pembrolizumab arms at 4.4 months compared to 2.8 months for the ipilimumab arm, (HR 0.58 [95% CI: 0.48, 0.70], p < 0.00001). There was also statistically significant difference in overall survival (OS) favouring the combined pembrolizumab arms compared to the ipilimumab arm, HR 0.65 (95% CI: 0.52, 0.83), p = 0.0002. The median follow-up time was 13.85 months, and the median OS was not reached in all three treatment arms.
The safety profile of pembrolizumab in this population is considered acceptable in the context of the treatment of metastatic melanoma. Overall, the incidence of drug related grade 3-5 adverse reactions and drug related serious adverse reactions were higher in the ipilimumab arms compared to the pembrolizumab arms. In addition, the grade 3-4 immune mediated adverse reactions were also lower in the pembrolizumab treatments arms. Immune mediated adverse reactions that are associated with PD-1 blocking antibodies including pneumonitis, colitis, hepatitis, nephritis, endocrinopathies, and infusion related reactions are labeled in the Product Monograph with appropriate instructions for medication discontinuation, dose holding and corticosteroid treatment.
Overall the benefit/risk analysis is considered favourable for the use of pembrolizumab in patients with unresectable or metastatic melanoma who have not received prior treatment with ipilimumab.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.