Regulatory Decision Summary for OPDIVO

Expression of PD-L1 and PD-L2 by tumours such as melanoma or on other cells in the tumour microenvironment allows tumours to evade immune-mediated destruction. Programmed death-1 is expressed at high levels by tumour infiltrating lymphocytes in melanoma and other tumours. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Nivolumab is a fully human monoclonal immunoglobulin G4 (IgG4) antibody (HuMAb) that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

The pivotal trial submitted in support of the proposed indication demonstrated a clinically and statistically significant improvement in overall survival (OS) in patients treated with Opdivo compared to patients treated with dacarbazine, with a hazard ratio (HR) of 0.42 [99.79% CI: 0.25, 0.73, p < 0.0001]. The median OS was 10.84 months in the dacarbazine group and was not reached in the Opdivo group. Statistically significant improvements were also seen in the relevant secondary endpoints of progression free survival and overall response rate in the Opdivo compared to the dacarbazine treatment arm. The safety profile was considered acceptable in the context of the treatment of metastatic melanoma. There were fewer deaths in the nivolumab group (22.8%) than in the dacarbazine group (46.8%), and the majority of deaths were attributed to disease progression. Immune mediated adverse events that are associated with PD-1blocking antibodies including endocrinopathies, colitis, hepatitis, pneumonitis, nephrotoxicity and rash are labeled in the Product Monograph with appropriate instructions for medication discontinuation, dose holding and corticosteroid treatment.

Overall the benefit/risk analysis is considered favourable for the use of Opdivo for the treatment of unresectable or metastatic BRAF V600 wild-type melanoma in previously untreated patients.

For more information on Health Canadas decision, please view the Summary Basis of Decision.