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.
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What was the purpose of this submission?
This supplemental new drug submission reviewed clinical efficacy and safety data for a new indication for Keytruda from a Phase III clinical trial. Based on this review, market authorization for the use of Keytruda (pembrolizumab) for the treatment of metastatic non-small cell lung cancer as monotherapy, in adults whose tumours have high PD-L1 expression (Tumour Proportion Score ≥ 50%), as determined by a validated test, with no EGRF or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC, was granted under a Notice of Compliance.
Why was the decision issued?
The study reviewed for the new Keytruda indication was KEYNOTE-024, which was a multicenter, open-label randomized, controlled trial for patients with metastatic NSCLC and a PD-L1 expression tumour proportion score (TPS) of 50% or greater by an immunohistochemistry assay, and no prior systemic treatment for metastatic NSCLC. Patients were randomized (1:1) to receive Keytruda (pembrolizumab) 200 milligrams (mg) intravenously every 3 weeks or investigators choice of any one of six platinum-containing chemotherapy regimens. At the second interim analysis, for the primary endpoint of progression free survival (PFS),a statistically significant difference was demonstrated in the median PFS favouring the Keytruda arm at 10.3 months compared to 6.0 months for standard of care chemotherapy [HR 0.50 (95% CI: 0.37, 0.68), p <0.001]. The secondary endpoint was overall survival. The median duration of follow up was 11 months. The median OS had not been reached for either arm but the OS difference achieved statistical significance favouring the Keytruda arm [HR 0.60 (95% CI: 0.41, 0.89), p-value = 0.005].
The safety profile of Keytruda (200 mg Q3W) in this population is considered acceptable in the context of the treatment of metastatic NSCLC. The incidence of drug related grade 3-5 adverse events and drug related serious adverse events was higher in the standard of care chemotherapy arm compared to the Keytruda arm. Immune mediated adverse reactions that are associated with PD-1 blocking antibodies including pneumonitis, colitis, nephritis, myositis, pancreatitis, endocrinopathies, and infusion related reactions are labeled in the PM with appropriate instructions for medication discontinuation, dose holding and corticosteroid treatment.
Overall the benefit/risk analysis is considered favourable for the use of Keytruda for the treatment of metastatic NSCLC as monotherapy, in adults whose tumours have high PD-L1 expression [(Tumour Proportion Score (TPS) ≥50%)] as determined by a validated test, with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC.
Based on the evaluation of the data submitted, and as labelled, the following indication for Keytruda: "treatment of metastatic non-small cell lung carcinoma (NSCLC) as monotherapy, in adults whose tumours have high PD-L1 expression [(Tumour Proportion Score (TPS) ≥50%)] as determined by a validated test, with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC," complies with the Food and Drug Regulations. A Notice of Compliance was recommended.
Decision issued
Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.