Regulatory Decision Summary for Imfinzi

The purpose of this supplemental new drug submission was to seek market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Imfinzi (durvalumab), as monotherapy or in combination with tremelimumab, for the treatment of patients with unresectable hepatocellular carcinoma (uHCC).

After evaluation of the submitted data package, Health Canada authorized Imfinzi for the following indications:

• Imfinzi in combination with tremelimumab is indicated for the first-line treatment of adult patients with unresectable hepatocellular carcinoma (uHCC) who require systemic therapy.

• Imfinzi, as monotherapy, is indicated for the first-line treatment of adult patients with uHCC who require systemic therapy.

Authorization for the use of Imfinzi (durvalumab), alone or in combination with tremelimumab, for the treatment of patients with uHCC, was based on results from an international, multi-centre, randomized, open-label trial. In this trial, patients (n = 1,171) with uHCC who were ineligible for locoregional therapy and who have not received prior systemic therapy were randomized in 1:1:1 to receive Imfinzi plus tremelimumab combination therapy (T300+D; n = 393), Imfinzi monotherapy (D; n = 389), or sorafenib (S; n = 389).

The primary efficacy endpoint was overall survival (OS). Both T300+D and D showed a statistically significant improvement in OS as compared to S, with the estimated hazard ratios (HRs) of 0.76 and 0.83 representing a 24% and 17% reduction in the risk of death, respectively, based on the adjusted analysis accounting for the observed baseline imbalances. The median OS was 16.4, 16.6 and 13.8 months for T300+D, D, and S, respectively.

The most common adverse reactions (ADRs) reported in at least 10% of patients who were treated with Imfinzi in combination with tremelimumab were pruritus, rash, diarrhoea, abdominal pain, pyrexia, AST increased, and hypothyroidism. The most common ADRs reported in at least 10% of patients who were treated with Imfinzi alone were pruritus, rash, diarrhoea, abdominal pain, and AST increased. The safety finding of Imfinzi was consistent with the previous observations. The risks associated with the uses of Imfinzi and Imfinzi in combination with tremelimumab are adequately captured in the Product Monograph (PM).

In view of the OS improvement observed with Imfinzi alone and Imfinzi in combination with tremelimumab, and the manageable safety profile, the benefits outweigh the risks for the target patient population.

The recommended dose of the combination of Imfinzi plus tremelimumab is 300 mg of tremelimumab as a single dose, followed by Imfinzi 1,500 mg at Day 1 of Cycle 1. Continue Imfinzi 1,500 mg as a single agent every 4 weeks until disease progression or unacceptable toxicity. The recommended dose of the Imfinzi monotherapy is 1,500 mg of Imfinzi as a single agent every 4 weeks until disease progression or unacceptable toxicity. View the PM for details.

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

Following review and requested revisions, the final labelling and Product Monograph were considered acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Imfinzi (durvalumab) for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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