Sacituzumab tirumotecan, alone and in combination with pembrolizumab, compared with standard chemotherapy in patients with advanced hormone receptor-positive, HER2-negative breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue in which cells in the breast gland multiply uncontrollably. In hormone receptor-positive, HER2-negative breast cancer, the tumor cells have binding sites (receptors) for the hormones estrogen and/or progesterone, but do not express the HER2 receptor at elevated levels. This form of breast cancer is typically treated initially with anti-hormone therapy, often in combination with a CDK4/6 inhibitor, a drug that further slows tumor growth. If the disease progresses despite this treatment, chemotherapy is generally considered. Sacituzumab tirumotecan is a novel antibody-drug conjugate (ADC) that is being tested in this study for the treatment of this disease. This is a drug in which an antibody specifically binds to a certain protein on the surface of cancer cells and delivers a cell-toxic active ingredient coupled to it directly into the tumor cells to inhibit their growth. As part of the study, sacituzumab tirumotecan is sometimes combined with the drug pembrolizumab. Pembrolizumab is a checkpoint inhibitor (immunotherapy) that is already approved for the treatment of various other cancers (e.g., melanoma or lung cancer) and helps the body’s own immune system recognize and fight cancer cells. The goal of this Phase 3 study is to investigate the efficacy and safety of the new drug sacituzumab tirumotecan, both alone and in combination with pembrolizumab, compared to standard chemotherapy. In the study, patients will be randomly assigned to three groups. In study arm A, sacituzumab tirumotecan will be administered alone as an intravenous infusion. In study arm B, patients receive sacituzumab tirumotecan in combination with pembrolizumab, both administered as intravenous infusions. In study arm C (the control arm), a standard chemotherapy regimen selected by the study physicians is administered, either as an intravenous infusion or as a tablet. Treatment will continue as long as the disease does not progress. Pembrolizumab will be administered for up to approximately two years. The study is open-label (unblinded), meaning that both the patients and the study physicians know which treatment is being administered. The main goal (primary endpoint) of the study is the time until the disease progresses (progression-free survival, PFS) for up to approximately 38 months. Patients 18 years of age and older with hormone receptor-positive, HER2-negative breast cancer that is inoperable and locally advanced or metastatic (has spread to other parts of the body) are eligible to participate in this study. The disease must have progressed while on anti-hormone therapy in combination with a CDK4/6 inhibitor for the advanced or metastatic stage, and patients must also be eligible for chemotherapy and must not have received chemotherapy for the advanced or metastatic stage yet.