AstraZeneca and Daiichi Sankyo Announce Phase 3 DESTINY-Breast03 Trial Success: Enhertu Demonstrates Superior PFS Over Approved Therapy in Second-Line HER2-Positive Metastatic Breast Cancer

On August 9, 2021, AstraZeneca and Daiichi Sankyo jointly announced that their co-developed HER2-targeted antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) met its primary endpoint in the Phase 3 DESTINY-Breast03 clinical trial. Interim analysis demonstrated that, in patients with HER2-positive, unresectable or metastatic breast cancer who had received prior first-line therapy, Enhertu resulted in a highly statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with the approved active control. Additionally, compared with the active control, a trend toward improvement was also observed for the key secondary endpoint of overall survival (OS) in the trial. Relevant trial data will be presented at an upcoming medical conference and submitted to regulatory authorities worldwide.

The global, open-label DESTINY-Breast03 trial enrolled approximately 500 patients to evaluate the safety and efficacy of Enhertu (5.4 mg/kg) in patients with HER2-positive unresectable and/or metastatic breast cancer who had received initial treatment with trastuzumab and a taxane. In addition to meeting the primary efficacy endpoint of progression-free survival (PFS), Enhertu demonstrated a strong trend toward improved overall survival (OS) in a key secondary endpoint compared with the active control arm, although the data remain immature. Regarding safety, the safety profile of Enhertu observed in the trial was consistent with previous studies, with no new safety signals identified and no reported grade 4 or 5 treatment-related interstitial lung disease (ILD) events.

Enhertu is an antibody-drug conjugate (ADC) designed using Daiichi Sankyo’s proprietary DXd ADC technology platform. It consists of a humanized monoclonal antibody targeting HER2, linked via a cleavable tetrapeptide linker to a topoisomerase I inhibitor payload. The drug is currently being further evaluated in a comprehensive clinical development program assessing its efficacy and safety across a broad range of HER2-expressing cancers, including breast, gastric, lung, and colorectal cancers.

Breast cancer is one of the leading causes of cancer-related mortality among women worldwide. In 2020, over 2 million new breast cancer cases were diagnosed globally, resulting in nearly 685,000 deaths. Approximately 20% of these patients are HER2-positive. HER2 is a growth-promoting tyrosine kinase receptor protein expressed on the surface of various tumor cells, including those of breast, gastric, lung, and colorectal cancers. Overexpression of the HER2 protein, which may result from HER2 gene amplification, is typically associated with aggressive disease and a poor prognosis.

Enhertu (5.4 mg/kg) has been approved in the United States, Japan, the European Union, and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received two or more anti-HER2-based regimens. Additionally, Enhertu (6.4 mg/kg) has also been approved in Israel, Japan, and the United States for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously received a trastuzumab-based regimen.

References:

[1] Enhertu significantly improved progression-free survival in DESTINY-Breast03 head-to-head trial vs. trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. Retrieved August 9, 2021, from https://www.astrazeneca.com/media-centre/press-releases/2021/enhertu-head-to-head-trial-meets-primary-endpoint.html

[2] ENHERTU® Significantly Improved Progression-Free Survival in DESTINY-Breast03 Head-to-Head Trial Versus Trastuzumab Emtansine (T-DM1) in Patients with HER2 Positive Metastatic Breast Cancer. Retrieved August 9, 2021, from

https://www.businesswire.com/news/home/20210808005018/en/ENHERTU%C2%AE-Significantly-Improved-Progression-Free-Survival-in-DESTINY-Breast03-Head-to-Head-Trial-Versus-Trastuzumab-Emtansine-T-DM1-in-Patients-with-HER2-Positive-Metastatic-Breast-Cancer

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