Regulatory Decision Summary for Keytruda

This Supplement to a New Drug Submission (SNDS) was submitted by Merck Canada Inc. to support the following proposed indication: 

KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of adult patients with FIGO 2014 Stage III–IVA cervical cancer. 

This submission was filed under the Notice of Compliance with Conditions.

This SNDS was filed as part of Project Orbis as a Type C submission and Health Canada collaborated with the Food and Drug Agency (FDA) and the European Medicines Agency (EMA) for the review.

Authorisation was based on the results from the KEYNOTE-A18 trial, an ongoing, randomized, Phase 3, placebo-controlled, multisite, double-blind study of chemoradiotherapy with or without pembrolizumab in participants with high-risk locally advanced cervical cancer. Patients were randomized (1:1) to receive either chemoradiotherapy in combination with pembrolizumab followed by pembrolizumab alone or chemoradiotherapy in combination with placebo followed by placebo alone.  

Statistically significant improvements in both progression-free survival (PFS) and overall survival (OS) were demonstrated in the intent-to-treat (ITT) population who received chemoradiation in combination with pembrolizumab. However, subgroup analysis revealed that the survival benefit was primarily driven by patients with FIGO 2014 Stage III–IVA disease, with a PFS Hazard Ratio (HR) of 0.59 (95% confidence interval [CI]: 0.43–0.81) and OS HR of 0.58 (95% CI: 0.40–0.85).

The improved efficacy in the FIGO 2014 Stage III–IVA subgroup was accompanied by a higher incidence of Grade 3–5 adverse events and a prolonged treatment duration of up to two years. However, the safety profile was consistent with known risks of pembrolizumab, and immune-related adverse events were generally manageable.

The safety findings and risk mitigation measures are described in the Keytruda (pembrolizumab) Product Monograph. 

The benefit–risk profile of Keytruda is considered favorable only in the Stage III–IVA population. Therefore, a Notice of Compliance (NOC) is recommended for the treatment of patients with FIGO 2014 Stage III–IVA locally advanced cervical cancer (LACC) when used in combination with concurrent chemoradiotherapy (CCRT).

For more information on the conditions issued, please refer to the Notice of Compliance with conditions (NOC/c) Web site.

For further details, including dosing, please refer to the Keytruda Product Monograph approved by Health Canada and available through the Drug Product Database.