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?
The purpose of the submission is to seek marketing authorization for Keytruda (pembrolizumab) as monotherapy for the treatment of adult and pediatric patients with refractory or relapsed classical Hodgkin Lymphoma (cHL) under the Notice of Compliance with Condition (NOC/c) guidance. After evaluation of the submitted data package, Health Canada authorized with conditions Keytruda (pembrolizumab) for the following indication: Keytruda as monotherapy is indicated for the treatment of adult and pediatric patients with refractory or relapsed classical Hodgkin Lymphoma (cHL) who have failed autologous stem cell transplant (ASCT), or who are not candidates for multi-agent salvage chemotherapy and ASCT.
Why was the decision issued?
Authorization was primarily based on a randomized, open-label, active-controlled multicentre phase III trial in adult patients with relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL) who were not candidates for stem cell transplant. Keytruda dosed 200 mg every 3 weeks (Q3W) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS). The median PFS was longer in the Keytruda group versus the control brentuximab vedotin (BV) group (13.2 versus 8.3 months). The risk of disease progression or death was reduced by 35% in patients treated with Keytruda compared to BV. Objective response rate (ORR) was 66% in the Keytruda group versus 54% in the BV group. Median duration of response (DOR) was 20.7 months in the Keytruda group and 13.8 months in the BV group.
The safety findings in the study are generally consistent with the known safety profile of Keytruda. The most frequently reported adverse events (AE, ≥15% of participants) were diarrhea, pyrexia, hypothyroidism, upper respiratory tract infection, pruritus, cough, and fatigue. Serious adverse events (SAEs) occurred in 30% of patients in the Keytruda group. Pneumonitis was the leading cause of SAEs and AE leading to treatment discontinuation. AEs of special interest (AEOSIs), reflecting immune-mediated or possibly immune-mediated events, occurred in 36% of patients, with thyroid disorders, pneumonitis, and infusion reactions being the most commonly reported events. These safety findings are adequately described in the Product Monograph.
The efficacy and safety evidence in pediatric cHL patients is limited compared to adult patients. However, pediatric cHL has characteristics similar to adult cHL, for example, similar histology and general treatment strategies. The mechanism of action of pembrolizumab is expected to be similar for pediatric and adult cHL based on similar PD-L1 expression and ORRs reported in other studies. Therefore, the efficacy and safety evidence in adult cHL patients can be generalized to pediatric cHL patients. In addition, the sponsor has agreed to post-market commitments to further evaluate the safety of Keytruda in pediatric patients, including developmental effect.
The recommended dose of the drug is 200 mg in adult patients, and is 2 mg/kg (up to a maximum of 200 mg) in pediatric patients, to be administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Decision issued
Authorized; issued a Notice of Compliance (NOC) in accordance with the Food and Drug Regulations.