Regulatory Decision Summary for Keytruda (pembrolizumab)

The purpose of this submission was to seek authorization of Keytruda (Pembrolizumab) in combination with chemotherapy for the treatment of patients with locally advanced unresectable or metastatic biliary tract carcinoma.

After evaluation of the submitted data package, Health Canada authorized Keytruda for the following indication:

• Keytruda, in combination with gemcitabine-based chemotherapy, is indicated for the treatment of adult patients with locally advanced unresectable or metastatic biliary tract carcinoma (BTC).

Since 2015, Keytruda has been authorized by Health Canada for multiple indications including Hodgkin Lymphoma, Primary Mediastinal B-cell Lymphoma, urothelial carcinoma, bladder cancer, colorectal cancer, endometrial cancer, melanoma, non-small cell lung carcinoma, renal cell carcinoma, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, cervical cancer, and triple-negative breast cancer.

The market authorization was based on the results of a pivotal phase 3, randomized, double-blind, multicenter, placebo-controlled study in adult patients in patients with locally advanced unresectable or metastatic biliary tract cancers (BTC).

A statistically and clinically meaningful improvement in the primary efficacy endpoint of overall survival (OS) was demonstrated for patients randomized to the Keytruda + gemcitabine + cisplatin arm compared with the placebo + gemcitabine + cisplatin arm (hazard ratio: 0.83; 95% CI: 0.72-0.95).

The safety profile of Keytruda in combination with gemcitabine and cisplatin is consistent with the known safety profile for Keytruda and the safety profiles of the other components of the treatment regimen. While there were slightly elevated occurrences of serious drug-related adverse events (AEs), treatment discontinuation due to a serious drug-related AE, and death due to a drug-related AE in the Keytruda + gemcitabine + cisplatin arm, the increased rates were similar to those documented in other trials using combination therapy. Higher rates of adverse events of special interest (AEOSI), serious AEOSI, and grade 3-5 drug-related AEOSI were observed in the Keytruda + gemcitabine + cisplatin arm compared to the placebo + gemcitabine + cisplatin arm. The AEOSI are manageable in most cases and the risk can be mitigated by labeling. The modified Keytruda plus gemcitabine-based chemotherapy indication is expected to enable tailored treatment selection, balancing efficacy and safety based on available evidence.

The recommended dose of Keytruda in adults is either:

200 mg every 3 weeks, or

400 mg every 6 weeks

until disease progression, unacceptable toxicity or up to 24 months or 35 doses for 200 mg or 18 doses for 400 mg, whichever is longer, in patients without disease progression.

View the Product Monographs of Keytruda and chemotherapy agents for details.

The overall benefit-risk assessment is considered favourable for the authorized indication. A Notice of Compliance (NOC) is recommended.