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Device/Product name
Active Ingredient
Trastuzumab deruxtecan
Date of decision
Submission type
New biological entity
ATC codes
Approved for provisional registration
What was the decision based on
The decision was based on quality (chemistry and manufacturing), nonclinical (pharmacology and toxicology), clinical (pharmacology, safety and efficacy) and risk management plan information submitted by the sponsor. The benefit-risk profile of Enhertu was considered favourable for the therapeutic use approved.
What steps were involved in the decision process

Registration timeline

The following table summarises the key steps and dates for this application.

This evaluation was facilitated through Project Orbis, an initiative of the United States (US) Food and Drug Administration (FDA) Oncology Center of Excellence (OCE). Under this project, the FDA and the TGA collaboratively reviewed the application. This innovative evaluation process provided a framework for process alignment and management of evaluation issues in real-time across jurisdictions.

Each regulator agency maintained its regulatory process to make independent decisions about the approval (market authorisation).

Description Date
Designation (Provisional) 22 July 2020
Submission dossier accepted and first round evaluation commenced 2 November 2020
First round evaluation completed 30 April 2021
Sponsor provides responses on questions raised in first round evaluation 1 June 2021
Second round evaluation completed 12 July 2021
Delegate's overall benefit-risk assessment 27 August 2021
Sponsor's pre-Advisory Committee response Not applicable
Advisory Committee meeting Not applicable
Registration decision (Outcome) 5 October 2021
Completion of administrative activities and registration on ARTG 8 October 2021
Number of working days from submission dossier acceptance to registration decision* 190

*Statutory timeframe for standard applications is 255 working days

Date of entry onto ARTG
Original publication date
Black triangle scheme
Yes. As a provisionally registered product, this medicine will remain in the Black Triangle Scheme for the duration of its provisional registration.
Dose forms
Powder for injection
100 mg
Other ingredients
Histidine, histidine hydrochloride monohydrate, sucrose and polysorbate 80.
Pack sizes
Routes of administration
Intravenous infusion

The recommended dose of Enhertu is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21 day cycle) until disease progression or unacceptable toxicity.

Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of Enhertu per guidelines provided in the Product Information.

For further information refer to the Product Information.

Pregnancy category
DDrugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.The use of any medicine during pregnancy requires careful consideration of both risks and benefits by the treating health professional. This must not be used as the sole basis of decision making in the use of medicines during pregnancy. The TGA does not provide advice on the use of medicines in pregnancy for specific cases. More information is available from obstetric drug information services in your State or Territory.
What was approved

Enhertu (trastuzumab deruxtecan) was approved for the following therapeutic use:

Enhertu is indicated for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti HER2-based regimens.

This indication is approved via the provisional approval pathway, based on overall response rate and duration of response. Full registration for this indication depends on verification and description of clinical benefit in a confirmatory trial.

What is this medicine and how does it work
Trastuzumab deruxtecan, is a human epidermal growth factor receptor 2 (HER2) targeted antibody-drug conjugate (ADC). The antibody is a humanised anti‑HER2 immunoglobin G1 (IgG1) attached to deruxtecan, a topoisomerase I inhibitor bound by a tetrapeptide based cleavable linker. The ADC is stable in plasma under in vitro conditions. Following binding to HER2 on tumour cells, trastuzumab deruxtecan undergoes internalisation and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane permeable topoisomerase I inhibitor causes deoxyribonucleic acid (DNA) damage and apoptotic cell death. The topoisomerase I inhibitor, an exatecan derivative, is approximately 10 times more potent than 7‑ethyl‑10‑hydroxycamptothecin (SN38), the active metabolite of irinotecan.
What post-market commitments will the sponsor undertake
  • Enhertu (trastuzumab deruxtecan) is to be included in the Black Triangle Scheme. The Product Information (PI) and Consumer Medicines Information (CMI) for Enhertu must include the black triangle symbol and mandatory accompanying text for the product's entire period of provisional registration.
  • The Enhertu European Union (EU)-risk management plan (RMP) (version 1.0, dated 22 January 2021, data lock point (DLP) 1 August 2019), with Australian specific annex (ASA) (version 1.0 succession 3, dated 16 July 2021), included with Submission PM-2020-04659-1-4, and any subsequent revisions, as agreed with the TGA will be implemented in Australia.

    An obligatory component of risk management plans is routine pharmacovigilance. Routine pharmacovigilance includes the submission of periodic safety update reports (PSURs).

    Unless agreed separately between the supplier who is the recipient of the approval and the TGA, the first report must be submitted to TGA no later than 15 calendar months after the date of the approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of the approval letter, or the entire period of provisional registration, whichever is longer.

    The reports are to at least meet the requirements for PSURs as described in the European Medicines Agency's Guideline on Good Pharmacovigilance Practices (GVP) Module VII-Periodic safety update report (Rev 1), Part VII.B Structures and processes. Note that submission of a PSUR does not constitute an application to vary the registration. Each report must have been prepared within ninety calendar days of the DLP for that report.

  • Laboratory testing and compliance with Certified Product Details
    • All batches of Enhertu supplied in Australia must comply with the product details and specifications approved during evaluation and detailed in the Certified Product Details (CPD).
    • When requested by the TGA, the sponsor should be prepared to provide product samples, specified reference materials and documentary evidence to enable the TGA to conduct laboratory testing on the product. Outcomes of laboratory testing are published biannually in the TGA Database of Laboratory Testing Results and periodically in testing reports on the TGA website.

    Certified Product Details

    The Certified Product Details (CPD), as described in Guidance 7: Certified Product Details of the Australian Regulatory Guidelines for Prescription Medicines (ARGPM), in PDF format, for the above products should be provided upon registration of these therapeutic goods. In addition, an updated CPD should be provided when changes to finished product specifications and test methods are approved in a Category 3 application or notified through a self-assessable change.

  • Confirmatory trial data (as identified in the sponsor's plan to submit comprehensive clinical data on the safety and efficacy of the medicine before the end of the six years that would start on the day that registration would commence) must be provided.

    Specifically, the sponsor must conduct studies as described in the clinical study plan in Version 1.0 Succession 3 dated 16 July 2021 of the ASA. The following study report(s) should be submitted to the TGA:

    • DS8201-AU301, Study U301 (the DESTINY-Breast02 trial), the second half in 2022, and
    • DS8201-AU302, Study U302 (the DESTINY-Breast03 trial), the fourth quarter in 2021.
  • For all injectable products the PI must be included with the product as a package insert.

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