Regulatory Decision Summary for Opdivo

The purpose of this Supplement to a New Drug Submission (SNDS) for Opdivo (nivolumab) was to seek market authorization for Opdivo (nivolumab) for:

Opdivo, in combination with platinum-doublet chemotherapy, is indicated for the neoadjuvant treatment of adult patients with resectable NSCLC (tumours ≥4 cm or node positive) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by Opdivo as a single agent in the adjuvant setting after surgical resection (see 14 CLINICAL TRIALS).

Upon review of the submitted data package, Health Canada authorized Opdivo with the following modification to the indication:

Opdivo, in combination with platinum-doublet chemotherapy, is indicated for the neoadjuvant treatment of adult patients with resectable Stage II (>4 cm), IIIA, IIIB (T3-4N2) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by Opdivo as a single agent in the adjuvant setting after surgical resection (see 14 CLINICAL TRIALS).

The submission was classified as a Project Orbis Type B submission and Health Canada collaborated with the United States Food and Drugs Administration for the review.

A Notice of Deficiency (NOD) was issued by Health Canada due to insufficient overall survival (OS) data identified during the review. In response to the NOD, the sponsor submitted an updated OS analysis for the CHECKMATE-77T study which addressed the objections regarding the identified efficacy concerns.

Efficacy was evaluated in the pivotal CHECKMATE-77T study, a Phase 3, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of Opdivo versus placebo, in combination with platinum-based chemotherapy in the neoadjuvant setting, followed by adjuvant Opdivo or placebo monotherapy after surgery in patients with resectable stage IIA (>4 cm) to IIIB (T3N2 or T4N2) non-small cell lung cancer (NSCLC). The trial demonstrated statistically significant and clinically meaningful improvements in Event Free Survival (EFS) for patients in the Opdivo arm over patients in the placebo arm. At the interim analysis for EFS, the results achieved statistical significance with a hazard ratio (HR) of 0.58 (95% confidence interval [CI]: 0.43, 0.78; p<0.00025) representing a 42% reduction in the risk of an event for patients in the Opdivo arm. Descriptive analysis showed an improvement in pathological complete response rate and major pathological response rate for patients who received Opdivo versus placebo. A statistically significant survival benefit was not achieved for patients in the Opdivo arm over patients in the placebo arm at the time of the interim analysis for OS (HR of 0.85 [95% CI: 0.61, 1.18]).

The adverse event (AE) profile observed in patients treated with Opdivo in combination with platinum-based chemotherapy in the neoadjuvant setting followed by Opdivo as a single agent after surgery was consistent with the established safety profile for Opdivo, and as expected with its use in combination with chemotherapy. Known risks included hypothyroidism/thyroiditis, pneumonitis, hyperthyroidism, rash, nephritis, and colitis and were observed with a higher incidence in patients treated with Opdivo. No new safety signals were identified. The risks with this treatment regimen, and appropriate risk management strategies, have been adequately communicated in the Product Monograph.

Overall, the benefit-risk is positive for the approved indication when used under the conditions of use recommended in the approved Product Monograph. The EFS benefit, supported by secondary endpoints, is considered clinically meaningful evidence of benefit for the target patient population. The safety profile is considered acceptable in the context of the patient population and when used according to the instructions in the Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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