Regulatory Decision Summary for Imfinzi

Authorization was based on a randomized, open-label, active-controlled, multicenter phase 3 trial in adult patients with treatment-naïve extensive-stage small cell lung cancer (ES-SCLC). In the Imfinzi plus chemotherapy group, patients (n = 268) were treated with Imfinzi 1,500 mg in combination with etoposide and either carboplatin or cisplatin (EP regimen) every 3 weeks for 4 cycles, followed by Imfinzi monotherapy 1,500 mg every 4 weeks until disease progression or unacceptable toxicity. In the chemotherapy control group, patients (n = 269) were treated with the EP regimen alone for up to 6 cycles.

The primary efficacy endpoint supporting the proposed ES-SCLC indication was overall survival (OS). At the planned interim analysis, the study demonstrated a statistically significant improvement in OS in the Imfinzi plus EP group vs. EP group (p = 0.0047). The median OS was 13 months in the Imfinzi plus EP group and 10.3 months in the EP alone group; the hazard ratio (HR) was 0.73, corresponding to a 27% reduction in the risk of death in patients treated with Imfinzi plus EP compared with patients treated with EP alone. The OS improvement is considered clinically meaningful and represents substantial evidence of clinical benefit.

Virtually all patients experienced at least 1 adverse event (AE). The incidences of AEs were generally similar between the Imfinzi plus EP and EP groups. In the Imfinzi plus EP group, the most common adverse events (occurring in ≥10% of patients) were neutropenia, anemia, nausea, fatigue, alopecia, thrombocytopenia, leukopenia, decreased appetite, constipation, cough/productive cough, vomiting, and dyspnoea, and the most frequent serious AEs were febrile neutropenia, pneumonia, anemia, pancytopenia, chronic obstructive pulmonary disease and pneumonitis. Immune-mediated adverse reactions (imARs) were reported in 19.6% of patients treated with Imfinzi plus EP. The most commonly reported immune-mediated adverse reactions were hypothyroidism (9.1%) and hyperthyroidism (5.3%). Overall, the safety profile in the Imfinzi plus EP group were generally consistent with the known safety profiles of Imfinzi and EP, and is considered acceptable in the context of the first-line treatment for ES-SCLC. These safety findings were adequately described in the updated Imfinzi product monograph (PM). An updated Imfinzi Risk Management Plan (RMP) was assessed and considered acceptable by Health Canada, which provides measures for risk monitoring and mitigation in the post-market setting.

The benefit and risk profile of Imfinzi in combination with etoposide with carboplatin or cisplatin is considered positive for the first-line treatment of adult patients with ES-SCLC.

The recommended dose of Imfinzi in combination with EP is 1,500 mg in combination with EP every 3 weeks for 4 cycles, followed by 1,500 mg every 4 weeks as monotherapy until disease progression or unacceptable toxicity. Patients with a body weight of 30 kg or less must receive weight-based dosing, equivalent to Imfinzi 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 20 mg/kg every 4 weeks as monotherapy until weight increases to greater than 30 kg. View the Product Monograph for details.