Company: AZN
Filing Date: 2025-04-04
Form Type: 6-K
Source: 0001654954-25-003894
Chunk: 4

Company: ASTRAZENECA PLC
Filing Date: 2025-04-04
Form: 6-K
Chunk 4
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% of patients with HR-positive, HER2-negative metastatic breast cancer screened were determined to be HER2-low or HER2-ultralow. 6

Prior to the approval of Enhertu in HER2-low and HER2-ultralow metastatic breast cancer based on the DESTINY-Breast04 and DESTINY-Breast06 trials, there were no HER2-targeted therapies approved specifically for patients with HER2-low or HER2-ultralow expression. 12,13

#### DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus investigator's choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months. HER2 status in the trial was confirmed by a central laboratory and was performed on a tumour sample obtained at the time of initial metastatic diagnosis or later.

The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), overall survival (OS) in the HER2-low patient population and OS in the overall trial population. Other secondary endpoints include objective response rate, duration of response, time to first subsequent treatment or death, time to second subsequent treatment or death and safety.

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2-low and n=153 for HER2-ultralow) in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov .

#### Enhertu
Enhert