Regulatory Decision Summary for Opdualag

The purpose of this new drug submission was to seek market authorization for Opdualag (nivolumab and relatlimab), for use in the treatment of adult and pediatric patients (12 years and older and weighing at least 40 kg) with unresectable or metastatic melanoma.

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

Opdualag (nivolumab and relatlimab) is indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma who have not received prior systemic therapy for unresectable or metastatic melanoma.

The market authorization of Opdualag was based on the results of a pivotal Phase 2/3, randomized, double-blind study in adult patients with previously untreated unresectable or metastatic melanoma. The study was designed to permit enrollment of pediatric patients 12 years or older; however, no pediatric patients enrolled in the trial. Patients were randomized (1:1) to receive either Opdualag (nivolumab 480 mg and relatlimab 160 mg) by intravenous (IV) infusion every 4 weeks or nivolumab 480 mg by IV infusion every 4 weeks.

A statistically significant improvement in the primary endpoint of progression-free survival (PFS) was demonstrated for patients randomized to the Opdualag arm compared with the nivolumab arm (hazard ratio [95% confidence interval (CI)] = 0.75 [0.62, 0.92]), representing a clinically meaningful 5.5 month improvement in median PFS for Opdualag. The result of the final analysis of overall survival (OS) appears to be favourable for Opdualag but was not statistically significant (hazard ratio [95% CI] = 0.80 [0.64, 1.01]). A higher percentage of patients in the Opdualag arm (43%) compared with the nivolumab arm (33%) achieved an objective response.

The safety profile of Opdualag is generally consistent with that of other immune checkpoint inhibitor therapies. Severe, and in some cases fatal, immune-mediated adverse reactions can occur with Opdualag; however, these adverse reactions can be effectively managed in most cases.

The efficacy and safety of Opdualag in pediatric patients 12 years or older is supported by clinical trial data in adults and the results of population pharmacokinetic analyses that suggest nivolumab and relatlimab exposures in pediatric patients 12 years of age or older who weigh at least 40 kg are expected to result in similar safety and efficacy to that of adults. The pharmacokinetics of nivolumab and relatlimab, the course of unresectable or metastatic melanoma, and the safety profile from studies of other immune-checkpoint inhibitor therapies are sufficiently similar in adults and pediatric patients 12 years of age or older to justify extrapolation of data from adults treated with Opdualag to pediatric patients 12 years or older who weigh at least 40 kg.

Overall, Opdualag provides an effective first-line treatment option for adults and pediatric patients 12 years of age or older with unresectable or metastatic melanoma. When administered at the authorized dosage, Opdualag is expected to provide a clinical benefit with a manageable safety profile. The risks associated with Opdualag can be effectively managed in the post-market setting. The benefit/risk profile of Opdualag is considered favourable for the authorized indication.

The risk management plan for Opdualag was reviewed and the sponsor was requested to submit a Periodic Benefit-Risk Evaluation Report (PBRER) annually for 3 years upon granting of market authorization in Canada. Additionally, the sponsor agreed to submit to Health Canada for review, the results of a planned study of Opdualag use in pediatric lymphoma patients if data suggests the safety profile is not consistent with that of adult melanoma patients.