Daiichi Sankyo and AstraZeneca announced the U.S. FDA has granted accelerated approval to Enhertu (fam-trastuzumab deruxtecan-nxki) 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 in the metastatic setting.
This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The FDA approval of Enhertu was based on the phase 2 DESTINY-Breast01 trial. The single-arm, open-label, two-part trial enrolled 184 patients at more than 100 sites globally. All patients were diagnosed with HER2-positive unresectable and/or metastatic breast cancer and had been previously treated with trastuzumab emtansine. The primary endpoint of the trial was objective response rate, as determined by independent central review. The trial results showed Enhertu (5.4mg/kg) monotherapy resulted in a confirmed objective response rate of 60.3% including a 4.3% complete response rate (n=8) and a 56.0% partial response rate (n=103). A median duration of response of 14.8 months was demonstrated as of 1 August 2019. In addition, a median progression-free survival of 16.4 months, based upon a median duration of follow up of 11.1 months was published online in The New England Journal of Medicine.
The most common adverse reactions (greater than or equal to 20% of patients) were nausea, fatigue, vomiting, alopecia and constipation. Interstitial lung disease (ILD)/pneumonitis occurred in 9% of patients. Fatal outcomes due to ILD/pneumonitis occurred in six patients (2.6%) – two deaths previously reported in the Phase I trial and four deaths previously reported in the Phase II trial DESTINY-Breast01.
A regulatory submission has also been filed with Japan’s Ministry of Health, Labour and Welfare based on the DESTINY-Breast01 and Phase I trials.
AstraZeneca and Daiichi Sankyo are exploring the further potential of Enhertu in HER2-breast cancer with three ongoing Phase III trials.
AstraZeneca and Daiichi Sankyo entered into a global collaboration in March of 2019 to jointly develop and commercialize Enhertu worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for manufacturing and supply.
Enhertu (fam-trastuzumab deruxtecan-nxki)
Enhertu is a HER-2 directed antibody-drug conjugate. This targeted anti-cancer drug delivers a novel topoisomerase I inhibitor payload to cancer cells via a cleavable tetrapeptide-based linker attached to a monoclonal antibody. The antibody binds to specific HER2 targets expressed on cancer cells. The antibody-drug conjugate uses Daiichi Sankyo’s proprietary DXd ADC technology.
About HER2-positive breast canceraaaa
Approximately one in five breast cancers are HER2-positive. This disease remains incurable with patients eventually progressing after available treatments. HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poor prognosis in patients with breast cancer.