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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ATC code: L01XC18
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What was the purpose of this submission?
The purpose of the current submission is to seek marketing authorization of Keytruda (pembrolizumab), as monotherapy, for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 [Tumour Proportion Score (TPS) ≥ 1%] as determined by a validated test, with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC. The primary objective was to extend Keytruda monotherapy to NSCLC patients with TPS 1-49% since it was already authorized for first-line treatment of metastatic NSCLC patients with TPS ≥ 50%.
After evaluation of the submitted data package, Health Canada authorized Keytruda for the following indication:
"Keytruda as monotherapy is indicated for the first-line treatment of adults with metastatic non-small cell lung carcinoma (NSCLC) or stage III disease where patients are not candidates for surgical resection or definitive chemoradiation, expressing PD-L1 [Tumour Proportion Score (TPS) ≥ 1%] as determined by a validated test, with no EGFR or ALK genomic tumour aberrations.
A positive association was observed between the level of PDL-1 expression and the magnitude of the treatment benefit (See CLINICAL TRIALS)."
Why was the decision issued?
Authorization was based on data from a Phase 3, multicenter, international, randomized, open-label, controlled clinical study of the first-line Keytruda (pembrolizumab) monotherapy versus platinum-based chemotherapy in adult subjects with metastatic non-small cell lung carcinoma (NSCLC) or stage III disease where patients are not candidates for surgical resection or definitive chemoradiation, expressing PD-L1 [Tumour Proportion Score (TPS ≥ 1%)] with no EGFR or ALK genomic tumour aberrations. Subjects were randomized in a 1:1 ratio (637 patients in each arm) to receive Keytruda (200 mg, i.v. every three weeks) or 1 of 2 platinum-based chemotherapy regimens: carboplatin + paclitaxel or carboplatin + pemetrexed. Responses to the treatments were determined with radiographic imaging by the blinded independent central radiologist review (BICR) every 9 weeks for the first 45 weeks, and every 12 weeks thereafter.
Overall survival (OS, primary endpoint) between Keytruda monotherapy and chemotherapy was statistically tested in sequential order at 3 TPS cutpoints: ≥50%, ≥20% and ≥1%. The study met its primary endpoints for all three pre-specified TPS cutpoints. A positive association of clinical benefit and PD-L1 expression was observed and in the subgroup of patients with TPS 1-49%, overall survival benefit of Keytruda monotherapy in comparison with chemotherapy is 1.3 months. Although the OS benefit from this subgroup is moderate, other information support the use of Keytruda monotherapy in the clinical setting, including longer duration of the response in Keytruda monotherapy arm, better safety profile of Keytruda monotherapy in comparison with the combination therapy of Keytruda and chemotherapy. Furthermore, available information from the updated 5-year survival data from NSCLC patients with TPS 1-49% in KN-001 study displayed a clinical meaningful median survival and 5-year survival rate. The positive association between the OS benefit and PD-1L expression and its implication in the treatment of patients with TPS 1-49% are included in the PM. The safety profile is consistent with the known safety profile for Keytruda monotherapy.
It is concluded that overall benefit risk profile is considered favourable.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.