Daiichi Sankyo (TYO: 4568) and AstraZeneca (AZ, NASDAQ: AZN) jointly announced that their co-developed antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) has received FDA approval for the treatment of unresectable or metastatic hormone receptor (HR) positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 ultra-low (IHC 0 with membrane staining) breast cancer in adult patients. These patients must have their disease status determined by FDA-approved testing methods and have received at least one line of endocrine therapy for metastatic cancer with disease progression. The Phase III clinical trial results showed that Enhertu demonstrated superior efficacy compared to chemotherapy, with a median progression-free survival (PFS) exceeding one year.
Approval Based on DESTINY-Breast06 Trial
The approval is primarily based on the positive results of the Phase III DESTINY-Breast06 trial. This global, randomized, open-label study assessed the efficacy and safety of Enhertu (5.4 mg/kg) compared to investigator’s choice of chemotherapy in patients with HR-positive, HER2-low or ultra-low expression advanced or metastatic breast cancer. Participants had not received prior chemotherapy for advanced or metastatic disease and had received at least two lines of endocrine therapy for metastatic disease. The trial enrolled 866 patients, including 713 with HER2-low expression and 153 with HER2 ultra-low expression.
Clinical Trial Results
The analysis showed that Enhertu reduced the risk of disease progression or death by 36% compared to chemotherapy in patients with HER2-low or ultra-low expression metastatic breast cancer who had not received prior chemotherapy (HR=0.64; 95% CI: 0.54-0.76; p<0.0001). The median PFS was 13.2 months for patients randomized to Enhertu, compared to 8.1 months for the chemotherapy group. The confirmed objective response rate (ORR) was 62.6% in the Enhertu group, significantly higher than the 34.4% in the chemotherapy group. The efficacy results were consistent across HER2-low and ultra-low expression patients in exploratory analyses.
Safety Profile
The safety profile of Enhertu in DESTINY-Breast06 was consistent with previous clinical trials in breast cancer, with no new safety concerns identified.
Enhertu Background
Enhertu is an ADC therapy co-developed by AstraZeneca and Daiichi Sankyo. It is designed using Daiichi Sankyo’s proprietary DXd ADC technology platform, consisting of a humanized anti-HER2 monoclonal antibody linked via a tetrapeptide cleavable linker to a topoisomerase I inhibitor payload. Enhertu was first approved by the FDA in 2019 for the treatment of unresectable or metastatic HER2-positive breast cancer. In April 2024, the FDA approved the therapy for the treatment of unresectable or metastatic HER2-positive solid tumors in adult patients who have received prior treatment and have no satisfactory alternative treatment options. Enhertu is the first HER2-targeted ADC therapy with a tumor-agnostic indication.-Fineline Info & Tech
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