Regulatory Decision Summary for Keytruda SC

The purpose of this submission was to seek market authorisation, pursuant to section C.08.004 of the Food and Drugs Regulations for Keytruda SC, a new formulation of pembrolizumab intended for administration using the subcutaneous (SC) route, in all previously authorized indications to Keytruda (intravenous formulation of pembrolizumab). Keytruda SC provides an alternative route of administration of pembrolizumab.

Keytruda (pembrolizumab solution for intravenous [IV] infusion), as monotherapy or in combination with other agents (chemotherapy, biologics or radiation), is currently authorized in Canada for the treatment of adult and pediatric patients across multiple tumour types. The recommended dose in adults is 200 mg every 3 weeks (Q3W) or 400 mg every 6 weeks (Q6W) administered by IV infusion over 30 minutes for an extended treatment period.

The current submission provides data to support a subcutaneous (SC) formulation of pembrolizumab, with the brand name of Keytruda SC, to be administered via the SC route in a single injection of either 395 mg over 1 minute Q3W or 790 mg over 2 minutes Q6W. Authorization was supported by one pivotal clinical study, four supportive clinical studies, and population pharmacokinetic (PK) analyses.

The pivotal clinical study MK-3475A-D77 demonstrated that exposures to pembrolizumab following administration of Keytruda SC 790 mg Q6W was noninferior, based on Cycle 1 AUC_0-6wks and Cycle 3 (steady state) C_trough, compared with Keytruda 400 mg Q6W, both in combination with chemotherapy, in patients with treatment-naïve metastatic non-small cell lung cancer (NSCLC). The descriptive analysis of the clinical efficacy results showed noninferior objective response rates of Keytruda SC compared with Keytruda. The exposures of Keytruda SC 395 mg Q3W are generally consistent with corresponding exposures of Keytruda SC 790 mg Q6W as well as with Keytruda 200 mg Q3W. The extrapolation of indications across multiple tumour types, treatment settings and in pediatric patients (12 years and older) were supported by the results of population PK and exposure response analyses.

The safety profile of Keytruda SC is generally consistent with the known safety profile of Keytruda. No new safety signals were detected, except local injection-site reactions that were low in frequency and mild in severity. The immunogenicity of Keytruda SC is low and consistent with the immunogenicity profile of Keytruda.

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

The chemistry and manufacturing information submitted for Keytruda has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, it is expected that the established positive benefit-risk profile of Keytruda will be maintained with Keytruda SC when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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