Study of a New Antibody-Drug Conjugate in Patients with Hormone Receptor-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s general condition, the stage (extent) of the disease, the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the presence of the HER2 receptor on the cells (HER2-positive). In an advanced stage—for example, when breast cancer has already spread to other parts of the body (metastases)—the disease is often no longer curable. Hormone receptor-positive breast cancer is typically treated with anti-hormone therapy, which is often combined with so-called CDK4/6 inhibitors, as this combination can delay the progression of the disease. If the disease continues to progress despite this treatment, new treatment options are sought. Patritumab deruxtecan (also known as HER3-DXd) is a new antibody-drug conjugate that is not yet approved for the treatment of breast cancer. It consists of an antibody that specifically binds to the HER3 receptor on the surface of cancer cells and a cell-damaging active ingredient (topoisomerase I inhibitor), which is released after penetrating the cancer cell and destroys it.

The goal of this Phase 3 study is to investigate the efficacy and safety of Patritumab Deruxtecan compared to standard therapy. Patients will be randomly assigned to one of two study groups. In the treatment arm, patients will receive patritumab deruxtecan as an intravenous infusion every three weeks. In the control arm, patients will receive a treatment selected by their treating physicians, which will be administered either as an intravenous infusion or as a tablet. The study is open-label, meaning that both patients and medical staff know which treatment is being administered. The primary endpoints of the study are progression-free survival (the time until the disease progresses) and overall survival. In addition, quality of life and treatment tolerability will be assessed. The expected duration of the study is approximately 85 months.

Women and men aged 18 and older with hormone receptor-positive, HER2-negative, locally advanced, or metastatic breast cancer whose disease has progressed while receiving treatment with a CDK4/6 inhibitor and anti-hormone therapy are eligible to participate in this study. Surgery must not be available as a curative (healing) treatment option, and patients must not have previously received chemotherapy for advanced-stage disease.