Drug Trial: A Comparison of Sacituzumab Govitecan-hziy and Pembrolizumab as New Adjuvant Therapies Versus Standard Therapy for Triple-Negative Breast Cancer Following Pre-Treatment and Surgery

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). 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 determining the treatment plan.

If the disease is potentially curable, treatment often begins with a combination of chemotherapy and immunotherapy (neoadjuvant therapy) with the goal of shrinking the tumor. This is followed by surgery to remove the remaining tumor tissue. This is often followed by radiation therapy. It is possible that, despite this treatment, cancer cells may still remain in the breast or lymph nodes. This is referred to as residual disease. In this situation, the risk of recurrence is significantly increased. Additional therapy after the tumor has been removed is intended to kill any remaining cancer cells and reduce the risk of recurrence (adjuvant therapy). Adjuvant therapy following surgery is usually standard practice for triple-negative breast cancer due to the high risk of recurrence. It is recommended to continue immunotherapy with the PD-1 antibody pembrolizumab if it was already administered in combination with chemotherapy prior to surgery. This medication strengthens the immune system and helps the body’s own defense system recognize and fight any remaining cancer cells. If residual tumor is present, the chemotherapy drug capecitabine can also be used, which inhibits the growth of cancer cells.

A new therapeutic approach being investigated in this study in patients with residual tumors is the combination of pembrolizumab with the antibody-drug conjugate sacituzumab govitecan-hziy. This medication can specifically bind to cancer cells via the antibody sacituzumab and deliver the attached active ingredient directly into the cancer cells. It is already approved as a monotherapy for metastatic triple-negative breast cancer. It has not yet been approved for use in combination with pembrolizumab.

The goal of this Phase 3 study is to investigate the efficacy and safety of the combination of sacituzumab govitecan-hziy and pembrolizumab in patients with residual tumor following surgery, compared to the current standard of care (pembrolizumab alone or with capecitabine). To this end, patients will be randomly assigned to two groups. In the study arm, patients will receive sacituzumab govitecan-hziy on Days 1 and 8 of a 21-day cycle as an infusion via a venous access site. Pembrolizumab is administered on Day 1 of each cycle. In the control arm, patients receive the standard therapy selected by the treating medical staff, i.e., either pembrolizumab alone or in combination with capecitabine. Patients in both groups receive a maximum of 8 cycles (approximately 6 months). The study is open-label, which means that patients and healthcare providers know which treatment is being administered. The primary endpoint—the main focus of the study—is how long patients live without a recurrence of breast cancer after the start of treatment, over a period of up to 5 years. Overall, follow-up as part of the study will continue for up to 8 years.

Eligible participants include women and men aged 18 and older with triple-negative breast cancer who still have detectable residual tumor in the breast or lymph nodes following neoadjuvant treatment and surgery. If radiation therapy is or was indicated, patients must have received it and recovered from it. The disease must not have metastasized yet, and patients must not have a BRCA mutation. Certain medications used in prior treatment of the disease (e.g., anti-hormone therapies lasting longer than 4 weeks, HER2-targeted therapies, or certain topoisomerase inhibitors) may exclude patients from the study.