Regulatory Decision Summary for Keytruda

The purpose of this Supplemental New Drug Submission (SNDS) was to seek market authorization for Keytruda (pembrolizumab), in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma (MPM).

After evaluation of the submitted data package, Health Canada authorized Keytruda for the first-line treatment of adult patients with unresectable advanced or metastatic MPM in combination with pemetrexed and platinum chemotherapy.

This submission was reviewed as part of Project Orbis.

Authorization was based on the results of KEYNOTE-483, a phase 3, randomized, open-label trial of Keytruda in combination with chemotherapy in adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). Patients were randomized (1:1) to receive either Keytruda in combination with pemetrexed and platinum-based chemotherapy (N = 222) or pemetrexed and platinum-based chemotherapy alone (N = 218).

A statistically significant improvement in the primary efficacy endpoint of Overall Survival (OS) was demonstrated for patients who received Keytruda in combination with chemotherapy compared to patients who received chemotherapy alone (Hazard Ratio = 0.79, 95% confidence interval: 0.64, 0.98, representing an estimated 21% reduction in the risk of death). The median OS was 17.3 months in the Keytruda treatment arm compared to 16.1 months in the chemotherapy treatment arm.

The safety profile of Keytruda in combination with pemetrexed and platinum-chemotherapy is consistent with the known safety profiles for Keytruda and the chemotherapy components. The most common treatment-related adverse events (≥ 20%) included fatigue, diarrhea, nausea, vomiting and stomatitis. The safety findings and risk mitigation measures are described in the Keytruda Product Monograph.

Overall, the benefit-risk profile of Keytruda, in combination with pemetrexed and platinum chemotherapy, is favourable for adult patients with unresectable advanced or metastatic MPM when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

The recommended dose of Keytruda for adults with advanced unresectable or metastatic MPM 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. Keytruda is administered in combination with pemetrexed and platinum chemotherapy for up to 6 cycles followed by Keytruda monotherapy.

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

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

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