Regulatory Decision Summary for OPDIVO

Opdivo is a fully human monoclonal immunoglobulin G4 (IgG4) antibody that is a highly specific programmed death-1 (PD-1) immune checkpoint inhibitor that blocks the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2. Opdivo was first authorized in Canada for use in the treatment of a melanoma subpopulation (BRAF V600 wild-type).

This market authorization was based on two pivotal trials, one in patients with metastatic squamous non-small cell lung cancer (SQ NSCLC) who had experienced disease progression during or after a prior platinum-based chemotherapy regimen and one in patients with metastatic non-squamous non-small lung cell cancer (NSQ NSCLC) who had experienced disease progression during or after one prior platinum-based chemotherapy regimen, where an additional line of therapy was allowed for patients with a known EGFR mutation or ALK translocation. Opdivo demonstrated a clinically and statistically significant improvement in overall survival (OS) compared to docetaxel treated patients in both trials. In SQ NSCLC, the improvement in overall survival (OS) compared to docetaxel was 3.2 months with the reduced risk of death by 41%. For NSQ NSCLC, there was the reduced risk of death by 27%, however, the Kaplan-Meier (K-M) curves for OS appear to separate only after approximately 7 months (favouring nivolumab) and the shape of the K-M curve appears consistent with a type of apparent delay in effect that can be observed clinically with immuno-oncology drugs.

In both pivotal trials subjects were enrolled regardless of PD-L1 expression status and the pre-study PD-L1 expression status was not used as a stratification factor. In the SQ NSCLC study, survival benefit was observed regardless of PD-L1 expression status by all pre-defined expression levels (≥1%, ≥5% or ≥10%). For the NSQ NSCLC study, pre-study PD-L1 expression status showed an apparent association for benefit from nivolumab for all efficacy endpoints: in PD-L1 positive subjects, nivolumab demonstrated improved efficacy versus docetaxel across all efficacy endpoints (OS, ORR [objective response rate], PFS [progression-free survival]); in contrast, there were no meaningful differences in efficacy between the treatment groups in the PD-L1 negative subgroups by any expression level (<1%, <5% and <10%). The role of the PD-L1 expression status has not been fully elucidated.

The safety profile was considered acceptable in the context of the treatment of metastatic NSCLC. Important identified risks associated with nivolumab monotherapy are known to include immune-mediated adverse reactions of pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, endocrinopathies (for example, hypothyroidism and hyperthyroidism), and infusion reactions. The Product Monograph contains appropriate instructions for medication discontinuation, dose holding and corticosteroid treatment.

Overall the benefit/risk analysis is considered favourable for the use of Opdivo in the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy (patients with EGFR or ALK genomic tumour aberrations should have disease progression on a therapy for these aberrations prior to receiving Opdivo).