Company: AZN
Filing Date: 2025-12-16
Form Type: 6-K
Source: 0001654954-25-013970
Chunk: 3

Company: ASTRAZENECA PLC
Filing Date: 2025-12-16
Form: 6-K
Chunk 3
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 the surface of many types of tumours including breast cancer. 5 HER2 protein overexpression may occur as a result of HER2 gene amplification. 6 Approximately one in five cases of breast cancer are considered HER2-positive. 7

HER2-positive metastatic breast cancer is an aggressive disease driven by overexpression or amplification of HER2. 8 Approximately 10,000 patients are treated each year in the 1st-line HER2-positive metastatic setting in the US. 9 While HER2-targeted therapies have improved outcomes, prognosis remains poor with most patients experiencing disease progression within two years of 1st-line treatment with THP, which has been the standard of care for more than a decade. 6,10-12 Approximately 25% to 30% of patients do not receive any treatment following 1st-line therapy due to discontinuation or death. 13-15

#### DESTINY-Breast09
DESTINY-Breast09 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4 mg/kg) either alone or in combination with pertuzumab versus standard of care THP as a 1st-line treatment in patients with HER2-positive metastatic breast cancer.

Patients were randomised 1:1:1 to receive either Enhertu monotherapy with a pertuzumab matching placebo; Enhertu in combination with pertuzumab; or THP. Randomisation was stratified by prior treatment ( de novo metastatic disease versus progression from early-stage disease), hormone receptor (HR) status and PIK3CA mutation status.

The primary endpoint of DESTINY-Breast09 is PFS as assessed by blinded-independent central review in the Enhertu monotherapy and Enhertu combination arms. Secondary endpoints include investigator-assessed PFS, overall survival, objective response rate, duration of response, pharmacokinetics and safety. The investigational arm assessing Enhertu monotherapy versus THP remains blinded to patients and investigators and will continue to the final PFS analysis.

DESTINY-Breast09 enrolled 1,157 patients across multiple sites in Africa, Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov .

#### Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo's proprietary DXd ADC Technology, Enhertu is the lead ADC in the onc