Sacituzumab tirumotecan in combination with pembrolizumab and chemotherapy as a new neoadjuvant treatment for early-stage, triple-negative, or hormone receptor-low-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 is determined, among other factors, by the characteristics of the tumor cells, particularly the presence of hormone receptors (estrogen and progesterone receptors) and the HER2 receptor. If all three receptors are absent, the cancer is referred to as triple-negative breast cancer (TNBC), which is considered particularly difficult to treat due to a lack of targets for targeted therapies. In early stages with a high risk of recurrence, treatment usually begins before surgery (neoadjuvant) with a combination of chemotherapy and the immunotherapy drug pembrolizumab, an immune checkpoint inhibitor that is already approved for this treatment in triple-negative breast cancer and supports the body’s own immune system in fighting cancer cells. The drug sacituzumab tirumotecan, which was also investigated in this study, is a so-called antibody-drug conjugate consisting of an antibody that specifically binds to cancer cells and delivers a cell-killing agent directly into the tumor cell. It is administered as an intravenous infusion and has not yet been approved in Europe.

The goal of this Phase 3 study is to investigate whether the additional administration of the new drug sacituzumab tirumotecan before surgery leads to a better response and can reduce the risk of disease recurrence compared to the current standard of care. Patients will be randomly assigned to one of two treatment groups. The study is open-label, meaning that both the patients and the study physicians know which treatment is being administered. In the study arm, patients first receive sacituzumab tirumotecan together with pembrolizumab, followed by chemotherapy with carboplatin and paclitaxel in combination with pembrolizumab, before undergoing surgery (and possibly radiation therapy). In the control arm, patients receive the current standard chemotherapy regimen consisting of carboplatin, paclitaxel, an anthracycline, and cyclophosphamide, each in combination with pembrolizumab, followed by surgery (and possibly radiation therapy). In both study arms, treatment with pembrolizumab will continue after surgery. If tumor remnants are still detectable in the surgically removed tissue, additional drug treatment may be administered at the discretion of the study physicians. The main objectives (primary endpoints) of the study are pathological complete remission at up to 30 weeks—that is, no evidence of cancer cells in the surgically removed tissue after treatment— and event-free survival for up to 92 months (the period during which no specific adverse event occurs after the start of treatment).

Women and men aged 18 and older with early-stage, non-metastatic triple-negative breast cancer or hormone receptor-low-positive, HER2-negative breast cancer with a high risk of recurrence, who have not previously received treatment for this disease, are eligible to participate in this study.