NEW YORK – AstraZeneca and Daiichi Sankyo on Tuesday said the US Food and Drug Administration accepted their biologics license application seeking approval for the HER2-targeted antibody-drug conjugate Enhertu (trastuzumab deruxtecan) as a treatment for patients with advanced HER2-low or HER2-ultralow breast cancer.
The FDA granted the BLA priority review and expects to issue a decision on the application in the first quarter of 2025.
The companies submitted data from the Phase III DESTINY-Breast06 trial, which included patients with hormone receptor (HR)-positive HER2-low or -ultralow advanced or metastatic breast cancer who had received prior endocrine therapy in the metastatic setting but had not had prior chemotherapy.
Traditionally, breast cancer patients have been classified as having either HER2-positive or -negative tumors based on HER2 expression levels. However, in the DESTINY-Breast04 trial, which led to Enhertu's approval in the US in 2022 for HER2-low metastatic breast cancer patients, a new HER2-low category emerged, defined as a HER2 immunohistochemistry expression score of 2+ and a negative in situ hybridization test or an IHC 1+ score.
In DESTINY-Breast06, researchers included the additional HER2-ultralow category, defined as a HER2 expression score of greater than 0 and less than 1 or an IHC 0 result with membrane staining. Advanced breast cancer patients with HER2-low or -ultralow tumors received either Enhertu or chemotherapy in the trial.
At the American Society of Clinical Oncology's annual meeting in June, researchers reported that, in this trial, treatment with Enhertu was associated with a 37 percent lower risk of disease progression or death compared to chemo. The median progression-free survival for the Enhertu group was 13.2 months versus 8.1 months for the chemotherapy arm. Patients with HER2-low and HER2-ultralow expression had comparable results. In a prespecified exploratory analysis, patients with HER2-ultralow expression on Enhertu had a 13.2-month median progression-free survival compared with 8.3 months for the control group.
With Enhertu's 2022 approval in the HER2-low setting, the drug became available in the US for patients with unresectable or metastatic breast cancer who have received prior chemo in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemo. With the DESTINY-Breast06 data, AstraZeneca and Daiichi Sankyo are attempting to expand Enhertu's access to chemotherapy-naïve advanced breast cancer patients and broaden the biomarker-defined population eligible for this antibody-drug conjugate. Up to 90 percent of tumors classified as HER2-negative may be HER2-low or HER2-ultralow.
"This priority review highlights the potential to expand the existing indication of Enhertu in HER2-low metastatic breast cancer to include use in an earlier disease setting as well as in a broader patient population that includes HER2-ultralow," Ken Takeshita, global head of R&D at Daiichi Sankyo, said in a statement. "We look forward to working closely with the FDA with the goal of bringing Enhertu to more patients as quickly as possible."