New Drug DB-1303/BNT323 vs. Standard Chemotherapy for Metastatic, HER2-Low, Hormone Receptor-Positive Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue in which cells multiply uncontrollably. Treatment depends on various factors, including the patient’s general condition, tumor stage, growth rate (e.g., Ki-67 index), hormone receptor status (estrogen/progesterone receptors), and the presence of the HER receptor on the cancer cells. Advanced or metastatic, hormone receptor-positive breast cancer is typically treated with anti-hormone therapy, often in combination with so-called CDK4/6 inhibitors. If the disease progresses despite this treatment, chemotherapy is used.

DB-1303/BNT323 is a new, targeted drug that is not yet approved for the treatment of breast cancer in Germany. It consists of an antibody that binds to the HER2 receptor on cancer cells, even when the receptor is present at only low levels (“HER2-low”). Once inside the cancer cell, the drug releases a chemotherapeutic agent, causing the cancer cell to die. Some of the released substance can also reach neighboring cancer cells, even if they have very few or no HER2 receptors (bystander effect). The drug is not yet approved in Germany for the treatment of breast cancer. The goal is to achieve the greatest possible effect directly within the tumor while minimizing the impact on healthy tissue.

The goal of this Phase 3 study is to determine whether the drug DB-1303/BNT323 is more effective than chemotherapy. As part of the study, patients will be randomly assigned to two groups. Group 1 receives DB-1303/BNT323 as an infusion via a venous access every 3 weeks. Group 2 receives a single-agent chemotherapy selected by the treating physicians (capecitabine, paclitaxel, or nab-paclitaxel). The study is open-label, meaning that both the medical staff and the patients know which medications are being administered. Treatment is continued until the disease progresses or until side effects or other reasons require discontinuation. The primary endpoint of the study is the time from the start of the study until the first occurrence of disease progression, recurrence, or death from any cause.

Eligible participants include women and men aged 18 and older with advanced or metastatic, hormone receptor-positive, and “HER2-low” breast cancer. A prerequisite is that the disease has continued to progress while on anti-hormonal therapy, either within 6 months of starting the first anti-hormonal therapy with a CDK4/6 inhibitor in the metastatic stage or after at least two different anti-hormonal therapies in the advanced/metastatic stage. No chemotherapy for the metastatic disease may have been administered to date (previous chemotherapy before or after breast tumor surgery is permitted if the patients were disease-free for more than 12 months afterward). In addition, there must be at least one measurable tumor on imaging (computed tomography or magnetic resonance imaging).