Regulatory Decision Summary for Keytruda

Pembrolizumab is a highly selective, high affinity humanized recombinant IgG4 monoclonal antibody that binds to the PD-1 receptor and blocks its ability to bind to PD-L1 and PD-L2. By this mechanism, pembrolizumab re-activates tumour-specific cytotoxic T lymphocytes and restores their ability to kill tumour cells.

The pivotal phase 3, multicentre, randomized, open-label study comparing pembrolizumab therapy to single agent chemotherapy as second-line therapy in patients with recurrent or progressive metastatic urothelial carcinoma demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) of 2.9 months and a 27% reduction in the risk of death favouring pembrolizumab. The OS result was supported by a clinically meaningful objective response rate of 21% in both the pivotal trial and supporting cohort study. The risk of adverse events was generally less for patients receiving pembrolizumab compared to those receiving chemotherapy. More specifically, therapy-related severe (grade 3-5) adverse events were several-fold more common among chemotherapy-treated patients compared to those treated with pembrolizumab. No serious adverse events were reported in greater than or equal to 5% of pembroliuzmab-treated patients. However, several adverse events occurring in greater than or equal to 1% of pembrolizumab-treated subjects that exceeded the incidence in chemotherapy-treated patients include pneumonitis, colitis, urosepsis, and urinary tract obstruction. The adverse events were reported to be responsive to standard medical management.

The most current version of the Canadian Special Annex to the Risk Management Plan was also reviewed and approved. There were no identified risks specific to the Canadian population requiring more than routine risk minimization measures taken for immune-mediated adverse events and infusion-related events.

The benefit / risk assessment is considered favourable for pembrolizumab as second-line therapy for patients with locally advance or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of completing neoadjuvant or adjuvant platinum-containing chemotherapy. As a result, this submission was issued a Notice of Compliance.