Regulatory Decision Summary for Enhertu

The purpose of this Supplement to a New Drug Submission (SNDS) was submitted to seek market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Enhertu (trastuzumab deruxtecan) filed by AstraZeneca Canada Inc. for for the treatment of adult patients with unresectable or metastatic HER2-positive (defined as immunohistochemistry [IHC] 3+) solid tumours that have progressed following prior treatment or who have no satisfactory alternative treatment option.

After evaluation of the submitted data package, Health Canada authorized with conditions Enhertu for the following indication:

Enhertu as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options.

Marketing authorization with conditions was based on confirmed objective response rate (ORR) and duration of response (DOR) from three single-arm studies. An improvement in survival has not yet been established.

The submission was filed under the Notice of Compliance with Conditions (NOC/c) Guidance.

The submission was classified as a Project Orbis Type C submission and Health Canada collaborated with the United States Food and Drug Administration (FDA) for the review.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

The recommendation for marketing authorization of Enhertu was based on the results of three pivotal, multicenter, open-label Phase 2 studies in adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options. Patients received Enhertu 5.4 mg/kg every three weeks (Q3W) until disease progression, withdrawal of consent, toxicity, or death of any cause.

The primary efficacy outcome measure was confirmed objective response rate (ORR) and a secondary efficacy outcome measure included duration of response (DOR). All outcomes were assessed by independent central review (ICR) based on Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST v1.1). Analysis of efficacy data of 156 patients pooled from three studies showed a confirmed ORR of 54.5% across 14 tumour types, including 3 (1.9%) patients with complete response and 82 (52.6%) patients with partial response. Across tumor types, a median DOR of 9.8 months was observed. These efficacy results provide promising evidence of clinical benefit for adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options. While evidence of clinical benefit was observed, the response varied among individual tumour types and furthermore, the efficacy of Enhertu in several tumour types were evaluated in fewer than 20 patients. Thus, to verify clinical benefit, efficacy in terms of ORR and DOR from an additional 40 patients with HER2-positive (IHC 3+) solid tumours from an ongoing study will be evaluated.

The safety of Enhertu in patients with HER2-positive (IHC 3+) solid tumours was generally consistent with its established safety profile. Interstitial lung disease (ILD), an important identified risk of Enhertu, was observed, which is manageable in most cases. The Product Monograph adequately captures the risks of Enhertu with management strategies including dose reduction and modification.

Overall, Enhertu was shown to be a promising treatment option for adult patients with HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options. When administered at the authorized dosages, Enhertu is expected to provide a clinically meaningful benefit with a manageable safety profile. The risks associated with Enhertu can be managed by dose modification guidelines described in the Product Monograph. The benefit-risk profile of Enhertu is considered favourable for the authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance with Conditions - Qualifying Notice (NOC/c -QN) was recommended.

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

For more information on the conditions issued, please refer to the Notice of Compliance with conditions (NOC/c) Website

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

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