Regulatory Decision Summary for Keytruda

The purpose of this submission was to seek authorization for Keytruda (Pembrolizumab), a humanized antibody used in cancer immunotherapy, as monotherapy for the adjuvant treatment of adult patients with Stage IB (T2a ≥ 4 cm), II, or IIIA non-small cell lung cancer (NSCLC) who have undergone complete resection.

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

• Keytruda as monotherapy is indicated for the adjuvant treatment of adult patients with Stage IB (T2a ≥ 4 cm), II, or IIIA NSCLC who have undergone complete resection and platinum-based chemotherapy.

Since 2015, Keytruda has been authorized by Health Canada for multiple indications including melanoma, bladder cancer, head and neck squamous cell carcinoma, classic Hodgkin’s lymphoma, urothelial carcinoma, colorectal cancer, endometrial cancer, renal cell carcinoma, breast cancer, and esophageal squamous cell carcinoma, and metastatic NSCLC.

Authorization was based on the results of study KEYNOTE-091, a randomized, triple-blinded, placebo-controlled, multi-centre, phase 3 study. Patients (n = 1,177) with IB (T2a ≥ 4 cm), II, or IIIA NSCLC who had undergone complete resection were randomized to receive either Keytruda (n = 590) 200 mg or placebo (n = 587) every 3 weeks for about 1 year.

The primary efficacy endpoints were disease-free survival (DFS) in overall population or the PD-L1 strong positive [Tumor Proportion Score (TPS) ≥ 50%] population. The study demonstrated that adjuvant treatment with Keytruda provided a significant improvement in DFS compared with placebo in the overall population. In a subgroup analysis, a potential detrimental effect was observed with Keytruda treatment for patients who did not receive prior adjuvant chemotherapy. Patients without prior adjuvant chemotherapy are excluded from the authorized indication. The available immature data showed that overall survival favored Keytruda over placebo.

The safety finding was consistent with the previous observations except hypothyroidism (19.7%). Two fatal adverse reactions of myocarditis occurred in Keytruda-treated patients (see the Product Monograph). Myocarditis is an uncommon but potentially fatal immune-related adverse reaction following Keytruda treatment.

The recommended dose of Keytruda is 200 mg every 3 weeks or 400 mg every 6 weeks for up to one year or until disease recurrence or unacceptable toxicity.

With exclusion of patients who do not receive adjuvant chemotherapy, the benefit-risk balance is favorable for the recommended indication.