Regulatory Decision Summary for Imfinzi (durvalumab)

In the current supplement to a new drug submission (SNDS), the sponsor sought authorization for Imfinzi (durvalumab) in combination with tremelimumab and standard of care platinum-based chemotherapy in the first line treatment of adult patients with metastatic Non-small Cell Lung Cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumour aberrations.

Marketing authorization was based on the results of a Phase III randomized, open-label, comparative multi-centre global study that included three arms: Arm 1 – durvalumab + tremelimumab (D+T) + standard of care platinum-based chemotherapy (SoC); Arm 2 – an additional investigative treatment arm; and Arm 3 – SoC. The evaluation of efficacy to support the proposed indication relied on the comparison between Imfinzi in combination with tremelimumab and platinum-based chemotherapy (Arm 1) and platinum-based chemotherapy alone (Arm 3).

The endpoints assessed for efficacy were key secondary objectives of progression-free survival (PFS) and overall survival (OS). Statistically significant improvements in PFS and OS were observed for Arm 1 compared to Arm 3. At the time of primary analysis for PFS, the PFS Hazard Ratio (HR) was 0.72 (95% confidence interval [CI] 0.60, 0.86), translating into a 28% reduction in the risk of progression or death in Arm 1. The median PFS was 6.2 months in Arm 1 as compared to 4.8 months in Arm 3, representing an estimated improvement in median PFS of 1.4 months. At the time of primary analysis for OS, the OS HR was 0.77 (95% CI 0.65, 0.92), translating into a 23% reduction in the risk of death in Arm 1. The median OS was 14.0 months in Arm 1 as compared to 11.7 months in Arm 3, representing an estimated improvement in median OS of 2.3 months.

The safety profile observed with D+T+SoC was generally consistent with the known safety profile for each of durvalumab and tremelimumab. The most common adverse drug reactions (ADRs) (any Grade, occurring in ≥10% of patients) for the Imfinzi in combination with tremelimumab and chemotherapy arm were anemia, nausea, neutropenia, decreased appetite, fatigue, diarrhea, rash, constipation, thrombocytopenia, vomiting, asthenia, pyrexia, pneumonia, alanine aminotransferase increased, aspartate aminotransferase increased, leukopenia, arthralgia, neutrophil count decreased, hypothyroidism, headache, pruritus, cough, and alopecia. The most commonly reported maximum Grade 3 or 4 events (occurring in ≥5% of patients) for the Imfinzi in combination with tremelimumab and chemotherapy arm were anemia, neutropenia, neutrophil count decreased, pneumonia, and thrombocytopenia. The risks associated with the use of Imfinzi in combination with tremelimumab and standard of care platinum-based chemotherapy are adequately captured in the Product Monograph (PM).

For the patients that are diagnosed with metastatic NSCLC, the net survival rate is <5%. In view of the improvements in terms of progression free survival and overall survival in patients treated with Imfinzi in combination with tremelimumab and platinum-based chemotherapy, and the manageable safety profile, the benefits outweigh the risks for the target population.

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