The investigational drug sacituzumab-tirumotecan, as monotherapy or in combination with pembrolizumab, compared with standard chemotherapy for triple-negative breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue in which the cells of the mammary gland multiply uncontrollably. Treatment depends on numerous factors, such as the patient’s overall health, the stage of the disease, and the surface characteristics of the cancer cells in terms of hormone receptors (estrogen, progesterone, and HER2 receptors). In triple-negative breast cancer, the tumor cells lack these hormone receptors for estrogen and progesterone, as well as the HER2 receptor. Since these characteristics represent important targets for targeted therapies, treatment options for triple-negative breast cancer are more limited, and conventional chemotherapy is primarily used. The disease may recur over time. In this case, it is referred to as a recurrence. The study drug sacituzumab-tirumotecan is a novel antibody-drug conjugate that specifically binds to cancer cells and delivers a cytotoxic agent directly into the tumor cells to inhibit their growth and kill the cancer cells. It is administered as an infusion via a venous access site (intravenously) and is not yet approved for treatment in Germany. Pembrolizumab is an immunotherapy that blocks an important inhibitory mechanism of the immune system (PD-1). This allows the body’s own immune system to better recognize and fight cancer cells. Pembrolizumab is already approved in Germany for the treatment of various forms of triple-negative breast cancer.

The goal of this Phase 3 study is to investigate the efficacy of the study drug sacituzumab-tirumotecan (alone or in combination with pembrolizumab) compared to a standard chemotherapy regimen selected by the study team. As part of the study, patients will be randomly assigned to three groups: Study arm A receives sacituzumab-tirumotecan alone, study arm B receives sacituzumab-tirumotecan in combination with pembrolizumab, and the control arm receives a standard chemotherapy regimen selected by the study team (for example, paclitaxel, nab-paclitaxel, or gemcitabine in combination with carboplatin). Before treatment with sacituzumab-tirumotecan, patients will receive prophylactic medications to prevent possible infusion-related reactions (e.g., a corticosteroid-like medication and an antihistamine). In addition, a corticosteroid-containing mouthwash is recommended to prevent mucositis. The study is open-label (not blinded), meaning that both the medical staff and the patients know which treatment is being administered. The primary endpoints of the study are progression-free survival (PFS)—the time from the start of the study until disease progression or death, up to 39 months—and overall survival, up to 61 months.

Women and men aged 18 and older with recurrent, inoperable, or metastatic triple-negative breast cancer who have not yet received drug therapy for the advanced disease are eligible to participate in this study. The tumor must express the surface marker PD-L1 only to a low degree (PD-L1 CPS < 10). If early-stage breast cancer was previously treated, that treatment must have been completed at least six months before the recurrence.