Regulatory Decision Summary for Imfinzi

This Supplemental New Drug Submission (SNDS) was filed to obtain market authorization for Imfinzi (durvalumab for injection) for the following new indication:

Imfinzi in combination with chemotherapy as neoadjuvant treatment, followed by Imfinzi as monotherapy after surgery, is indicated for the treatment of patients with resectable (tumours ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

After review, the following indication was authorized:

Imfinzi in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by Imfinzi as monotherapy after surgery, is indicated for the treatment of patients with resectable Stage II, IIIA, or IIIB (T3-4 N2) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Efficacy was evaluated in the AEGEAN trial, a double-blind, placebo-controlled, randomized, multi-centre global study designed to evaluate the efficacy and safety of durvalumab in combination with systemic neoadjuvant chemotherapy (either carboplatin plus paclitaxel, cisplatin (or carboplatin) plus gemcitabine, pemetrexed plus cisplatin or pemetrexed plus carboplatin) followed by durvalumab in the adjuvant setting versus placebo in combination with systemic neoadjuvant platinum-containing chemotherapy followed by placebo in the adjuvant setting for the treatment of adult patients with resectable Stage IIA-IIIB[N2] non-small cell lung cancer (NSCLC).

The AEGEAN trial met its two pre-specified primary endpoints for pathological complete response (pCR) and event-free survival (EFS). At the first two pre-specified interim analyses (IAs), pCR IA and EFS IA, a statistically significant improvement in the primary endpoints of pCR and EFS in the durvalumab plus chemotherapy arm compared to placebo plus chemotherapy were demonstrated. The pCR for treatment with durvalumab in combination with chemotherapy before surgery was 17.2% (95% Confidence Interval (CI): 13.5, 21.5) when compared to placebo in combination with chemotherapy 4.3% (95% CI: 2.5, 6.9). At the EFS IA, the hazard ratio (HR) was 0.68 (95% CI: 0.53, 0.88).

The study also includes key secondary endpoints of major pathological response (MPR), disease-free survival (DFS), and overall survival (OS). Regarding the key secondary endpoints, MPR also reached statistical significance in the durvalumab plus chemotherapy arm (34%) compared to placebo plus chemotherapy arm (14%). However, DFS was not statistically significant and, therefore, OS was not formally tested according to the statistical analysis plan.

The safety profile from the AEGEAN clinical trial was unremarkable and consistent with that from previous clinical trials involving durvalumab in combination with chemotherapy. As expected with the addition of a biologic drug to an existing chemotherapy regimen, there were more adverse events especially those leading to discontinuation, treatment delay and deaths in the durvalumab plus chemotherapy arm when compared to the placebo plus chemotherapy arm. No new safety signals were observed in the AEGEAN clinical trial and sufficient risk mitigation measures for using durvalumab in combination with platinum-containing chemotherapy in resectable NSCLC patients are adequately described in the Imfinzi Product Monograph.

An updated Risk Management Plan (RMP) for Imfinzi was reviewed by Health Canada and considered acceptable.

Overall, the benefit-risk profile is favourable for Imfinzi (durvalumab) in combination with platinum-based chemotherapy and the dosage strength for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) is recommended.

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