A Study of the Antibody Zanidatamab in Combination with Chemotherapy Compared to the Current Standard of Care for Metastatic HER2-Positive 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 overall health, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased expression of the HER2 receptor on the cells (HER2-positive). In HER2-positive breast cancer, the HER2 receptor acts as a binding site for growth factors that stimulate cell division. Because there is an increased number of these binding sites, the cancer cells divide and multiply more rapidly, which often leads to a more aggressive course of the disease. This characteristic also provides a target for treatment options. Through so-called targeted therapies, which specifically block or recognize the HER2 receptor, cancer cells can be targeted and combated. If the cancer has spread to other parts of the body and formed secondary tumors, it is referred to as metastatic breast cancer. The current standard of care at this stage of the disease consists of combination therapy using the HER2 antibody trastuzumab and chemotherapy. Another drug, trastuzumab deruxtecan (T-DXd), combines an antibody with a cytotoxic agent to destroy cancer cells even more precisely. A new active ingredient is zanidatamab, a so-called bispecific antibody. Unlike conventional antibodies, which block only one site on the HER2 receptor, zanidatamab binds to two different sites on the receptor on the surface of the tumor cell. This dual binding enhances the effect by not only blocking cell growth but also leading to the degradation of HER2 receptors. Zanidatamab is currently approved for the treatment of HER2-positive bile duct cancer.

The goal of this Phase 3 study is to investigate whether zanidatamab in combination with chemotherapy is more effective than the current standard of care, which consists of trastuzumab plus chemotherapy. Depending on individual suitability, the chemotherapy may consist of eribulin, vinorelbine, gemcitabine, or capecitabine and will be selected by the treating medical staff. Assignment to a treatment group is random; this is an open-label study, meaning that both patients and physicians are aware of which group—treatment or control—each participant belongs to. The primary endpoint—that is, the main objective—of the study is to delay disease progression (progression-free survival, PFS) and improve overall survival (OS).

Eligible participants include women and men aged 18 and older with HER2-positive, inoperable, or metastatic breast cancer who experienced disease progression while receiving trastuzumab deruxtecan (T-DXd) therapy or who were unable to tolerate the medication.