Regulatory Decision Summary for Opdivo
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of this supplemental new drug submission (SNDS) was to obtain authorization of Opdivo (nivolumab) for the new indication of Opdivo in combination with fluoropyrimidine and platinum containing chemotherapy, for the treatment of adult patients with advanced or metastatic gastric (GC), gastroesophageal junction (GEJC) or esophageal adenocarcinoma (EC).
Why was the decision issued?
Market authorization was primarily based on results of the pivotal phase 3, randomized, multicenter, open-label study (CA209649), of Nivolumab in combination with platinum and fluoropyrimidine containing chemotherapy in subjects with previously untreated advanced or metastatic gastric (GC), gastroesophogeal junction cancer (GEJC), or esophageal adenocarcinoma (EC). Patients (n = 1,581) were randomized into the nivo + chemo (n = 789) and chemo (n = 792) arms and treatment was administered until progressive disease, unacceptable toxicity, a maximum of 2 years for nivolumab, or patient withdrawal of consent, whichever occurred first. The chemotherapy regimens used in combination with Opdivo were XELOX (oxaliplatin, and capecitabine) every 3 weeks (Q3W) or FOLFOX (oxaliplatin, leucovorin, and fluorouracil) Q2W. At the pre-planned interim analysis Opdivo in combination with chemotherapy demonstrated a statistically significant improvement in overall survival (OS) (Hazard Ratio [HR]: 0.80 [99.3% Confidence Interval (CI): 0.68, 0.94]) in all randomized patients. Median OS was improved by 2.2 months and this survival benefit was supported by improved progression free survival.
The safety profile of nivolumab in combination with platinum and fluoropyrimidine containing chemotherapy was consistent with the know safety profiles of nivolumab, platinum chemotherapy, and fluoropyrimidine chemotherapy, and reflects the use of these therapies in combination. The most common drug-related adverse events (AEs) across both arms were nausea, diarrhea, peripheral neuropathy, anemia, fatigue, vomiting, neutropenia, decreased appetite, thrombocytopenia, and aspartate aminotransferase (AST) increased. Adverse reactions were generally manageable and no new safety concerns were identified for Opdivo.
The Canadian Product Monograph has been updated for the key safety and efficacy findings for the proposed combination use.
Based on the efficacy and safety results in the submission, the benefit/risk profile of Opdivo in combination with platinum and fluoropyrimidine containing chemotherapy for the treatment of GC, GEJC, and EC is considered positive.
Decision issued
Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations