Regulatory Decision Summary for Keytruda (pembrolizumab)

The purpose of this Supplement to a New Drug Submission (SNDS) is to seek the authorisation for Keytruda for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumours, as determined by a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.

After evaluation of the submitted data package, Health Canada authorized Keytruda for the indication as proposed above.

For other authorized indications for Keytruda, please refer to the Keytruda Product Monograph.

The authorisation was based on the results from clinical studies conducted in both adults and pediatric patients with various MSI-H/dMMR solid tumours.

The key data to support authorisation in adults were from KEYNOTE-158, a study of pembrolizumab in adults with various advanced MSI-H/dMMR solid tumours. While response rates varied across tumour types evaluated, the overall objective response rate was 33.8% and included 10.7% complete responders and 23.1% partial responders. The duration of response was deep and durable, with a median duration of response of 63.2 months, with 66% responders maintaining a response of over 5 years as estimated by Kaplan Meier analysis. These results are clinically meaningful for the proposed adult population who have failed prior therapy and have no alternative treatment options.

The key data to support authorisation in pediatrics were from KEYNOTE-051, a single arm study of pembrolizumab in various tumours and which included a cohort of pediatric patients with advanced MSI-H/dMMR solid tumours. There was only limited data available in pediatric patients (7 participants) and similar to adults, the responses were variable in that there were no classic responders (one patient had stable disease). However, one subject with a brain tumour had a radiographic complete response after pseudo-progression which was sustained for 15 months. A rationale for extrapolation of data from the adult studies to the pediatric population was also considered based on similarity in disease biology and in pharmacology/drug effect in MSI-H tumours. Despite the limited data in pediatrics, taken together, the data from pediatric study KEYNOTE-051 and the adult study KEYNOTE-158, along with the rationale for the extrapolation of the indication are considered meaningful in the proposed pediatric population who failed prior therapy and have no alternative treatment options.

The safety profile of Keytruda in adults and pediatrics were consistent with the known safety profile. There were some differences in the safety profile noted between the adult and pediatric populations comprising increased frequency of pyrexia (fever), vomiting, headache, abdominal pain and the laboratory differences in the rate of leukopenia, neutropenia and thrombocytopenia. The risk information has been captured in the Keytruda Product Monograph. Immune-mediated adverse reactions were observed, consistent with the safety profile of Keytruda. These adverse reactions can be managed in most cases and the Keytruda Product Monograph adequately captures these and other risks of treatment and includes strategies for the management of immune-mediated adverse reactions.

Overall, Keytruda provides a treatment option for adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumours, as determined by a validated test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. When administered at the authorized dosage, Keytruda is expected to provide a clinical meaningful benefit with a manageable safety profile. The risks associated with Keytruda can be effectively managed in the post-market setting based on current guidelines. The benefit/risk profile of Keytruda is considered favourable for the authorized indication.

An updated Risk Management Plan (RMP) for Keytruda was reviewed by Health Canada and considered acceptable.

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