Drug Trial: Sacituzumab Govitecan-hziy and Pembrolizumab (drugs) as a new first-line therapy compared to standard therapy for triple-negative, advanced, inoperable 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 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 presence of the HER2 receptor on the cells (HER2-positive). If none of these receptors are present, the cancer is referred to as triple-negative breast cancer.

The stage of the disease plays a decisive role in treatment decisions. In the locally confined stage (stages 1–2), the disease is limited to the breast. Treatment at this stage aims to completely cure the disease by combining chemotherapy and/or hormone therapy with surgery. In the locally advanced stage (stages 3–4), the tumor is already larger, lymph nodes are involved, and there may be secondary tumors elsewhere in the body (metastases). Surgery is usually no longer an option at this stage, and the goal is to “keep the disease at bay” for as long as possible using various treatments. Triple-negative breast cancer is generally more difficult to treat than other forms, as fewer treatment options are available. To date, the standard of care for untreated triple-negative breast cancer with detectable distant metastases has been chemotherapy using drugs from the anthracycline or taxane classes (+ bevacizumab). Sacituzumab Govitecan-hziy and pembrolizumab are novel drugs that are already approved for the treatment of triple-negative metastatic breast cancer when other standard therapies are no longer effective (sacituzumab Govitecan-hziy) or as first-line therapy (pembrolizumab). Sacituzumab Govitecan-hziy is an antibody-drug conjugate that specifically binds to cancer cells and releases the cancer-killing drug directly at the site. Pembrolizumab is a programmed death-ligand 1 (PD-L1) inhibitor that helps the immune system fight cancer cells.

The goal of this Phase 3 study is to investigate the efficacy and safety of treatment with Sacituzumab Govitecan-hziy in combination with pembrolizumab in a larger group of patients. As part of the study, patients will be randomly assigned to two groups. Group 1 will receive sacituzumab govitecan-hziy as an infusion via a venous line on Days 1 and 8 of a 21-day cycle. Pembrolizumab is administered on the first day of each cycle for a maximum of 35 cycles. Group 2 receives standard chemotherapy in combination with pembrolizumab.

The study is open-label, meaning that both medical staff and patients know which medications are being administered. Treatments and follow-up examinations as part of the study will take place over approximately 3 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease progresses again during therapy. Further follow-up will also take place (for up to a total of approximately 5 years).

Women and men aged 18 and older with locally advanced, inoperable, or metastatic breast cancer are eligible to participate in this study. For the study, the disease must be untreated, hormone receptor-negative, and HER2-negative. In addition, the cancer cells must express PD-L1.