First tumour agnostic HER2 directed ADC gets US approval

Antibody drug conjugate

Daiichi Sankyo and AstraZeneca’s Enhertu (fam-trastuzumab deruxtecan-nxki) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+) solid tumours.

Enhertu has been granted accelerated approval to treat patients who have received prior systemic treatment and have no satisfactory alternative treatment options.

The Food and Drug Administration (FDA) has cautioned that continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu is a specifically engineered HER2 directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by Daiichi Sankyo and AstraZeneca.

This latest approval means that Enhertu now has five approved indications, including for breast cancer.

Phase II clinical trial results

The approval was based on efficacy data in 192 adult patients with previously treated unresectable or metastatic HER2 positive (IHC 3+) solid tumours who were enrolled in one of three multicentre Phase II trials from the DESTINY clinical development programme.

In DESTINY-PanTumor02, overall response rate (ORR) was 51.4% and median duration of response (DOR) range was 19.4 months. In DESTINY-Lung01, ORR of 52.9% and median DOR range of 6.9 months was seen. In DESTINY-CRC02, ORR was 46.9% and median DOR range was 5.5 months.

“Until the approval of trastuzumab deruxtecan, patients with metastatic HER2 positive solid tumours have had limited treatment options,” said Funda Meric-Bernstam, Chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. “Based on the clinically meaningful response rates seen across clinical trials, this tumour-agnostic approval means that patients may now be treated with a HER2 directed medicine.”

As part of Project Orbis, Enhertu also is under regulatory review for the same indication by regulatory authorities in Australia, Brazil and Singapore.

The ADC is approved with boxed warnings for interstitial lung disease (ILD)/pneumonitis and Embryo-Fetal toxicity.

“As the first antibody drug conjugate to be granted a tumour agnostic indication, Enhertu is truly delivering on its potential across metastatic HER2 targetable tumours,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “This approval also elevates the importance of testing for biomarkers, including HER2, across a broad range of tumours to ensure these patients with advanced cancer who have few options know whether a targeted medicine might be right for them.”

Diana Spencer, Senior Digital Content Editor, DDW

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