Regulatory Decision Summary for Opdivo

This Supplemental New Drug Submission (SNDS) was submitted to seek an expanded indication for Opdivo for the treatment of patients diagnosed with Stage IIB or IIC melanoma.

After evaluation of the submitted data package, Health Canada authorized Opdivo for the following indication: Opdivo, as monotherapy, is indicated for the adjuvant treatment of adult patients with Stage IIB or IIC melanoma following complete resection.

The submission was classified as a Project Orbis Type C submission and Health Canada collaborated with United States Food and Drug Administration (FDA) for the review.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Authorization was based on the results of a Phase 3, randomized, double-blind, placebo-controlled, multicenter trial (CHECKMATE-76K) designed to assess the efficacy and safety of nivolumab versus placebo in the adjuvant treatment of patients with Stage IIB or IIC melanoma following complete resection. A total of 790 subjects were randomized 2:1 to the nivolumab arm (n = 526) and placebo arm (n = 264). The dosing regimen evaluated in the study for adults was 480 mg nivolumab monotherapy administered intravenously every 4 weeks (Q4W).

The study met the primary objective of demonstrating a statistically significant and clinically meaningful improvement in recurrence-free survival (RFS) with nivolumab treatment compared with placebo in all randomized patients. The median RFS was not reached in either treatment arm. The estimated hazard ratio (HR) was 0.42, representing a 58% reduction in the risk of recurrence or death with nivolumab.

The most commonly reported adverse events (AEs) (incidence ≥10%) in the nivolumab arm were fatigue, diarrhea, pruritus, arthralgia, nausea, rash, headache, hypothyroidism, asthenia and blood creatine phosphokinase increased. The immune-mediated adverse events (imAE) observed were similar to the established nivolumab monotherapy safety profile, and also similar across the pooled safety datasets. The majority of imAEs observed were low Grade (Grades 1-2) and manageable. No new safety signals were identified from the CHECKMATE-76K study, and the safety results observed was consistent with the established safety profile of nivolumab monotherapy. Overall, the safety profile of nivolumab is well characterized and clinically manageable by standard clinical practice. The risks and risk mitigation strategies have been communicated in the Product Monograph.

Based on the review of the results of the CHECKMATE-76K study, the evidence shows a positive benefit/risk profile for the use of nivolumab as an adjuvant treatment for adult with completely resected Stage IIB or IIC melanoma.

The recommended dose of nivolumab is 240 mg (30-minute IV infusion) Q2W or 480 mg (30-minute IV infusion) Q4W. Continue treatment as long as clinical benefit is observed or until treatment is no longer tolerated by the patient (unacceptable toxicity) for up to 1 year.

Overall, the benefit/risk profile of nivolumab monotherapy use for the treatment of adult patients with Stage IIB or IIC melanoma following complete resection is considered positive.

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