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:
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ATC code: L01XC18
Type of submission:
Control number:
What was the purpose of this submission?
The purpose of this submission was to seek authorization for a new indication of Keytruda (pembrolizumab) in combination with pemetrexed and platinum chemotherapy for the treatment of metastatic non-squamous Non-Small Cell Lung Carcinoma (NSCLC), in adults with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC.
Keytruda has been granted market authorization (with or without conditions) for the treatment of patients with unresectable or metastatic melanoma, metastatic NSCLC, locally advanced or metastatic urothelial carcinoma, refractory or relapsed classic Hodgkin lymphoma, and refractory primary mediastinal B-cell lymphoma.
Why was the decision issued?
Authorization was based on the pre-defined interim analysis results from KEYNOTE-189 study, an international, multi-center, randomized, double-blind, placebo-controlled trial. Patients (N = 616) with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations received either Keytruda in combination with pemetrexed and platinum chemotherapy (treatment arm) or pemetrexed, and platinum chemotherapy (control arm).
Primary efficacy endpoints were Overall Survival (OS) and Progression-Free Survival (PFS). Keytruda in combination with pemetrexed and platinum chemotherapy provides statistically significant improvement in OS and in PFS compared with the control arm. The median OS was not reached for the treatment arm and was 11.3 months for the control arm. The median PFS was favouring the treatment arm at 8.8 months compare to 4.9 months for the control arm.
The overall safety profile is comparable to the established Keytruda data from prior clinical trials with other indications. The common drug-related adverse events reported in at least 20% of patients were nausea (46.2%), anemia (38.0%), fatigue (33.1%), neutropenia (24.9%), and decreased appetite (20.7%). The incidences of discontinuations of any drug due to adverse events were higher in the treatment arm compared with the control arm. The most common treatment-related adverse events leading to study drug discontinuation were acute kidney injury and pneumonitis. The event rates of febrile neutropenia and nephritis were higher in the treatment arm compared with the control arm.
Key safety and efficacy findings were adequately labeled in Keytruda product monograph.
The recommended dose of Keytruda is 200 mg fixed dose administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity or up to 24 months in patients without disease progression.
Overall results from KEYNOTE-189 study are considered sufficient to establish a positive risk / benefit assessment in the sought indication for the first line treatment of metastatic non-squamous NSCLC in combination with pemetrexed and platinum therapy.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.