New combination therapy with pembrolizumab and sacituzumab-tirumotecan (a new drug) for triple-negative breast cancer with residual tumor following surgery

Breast cancer (mammary carcinoma) is one of the most common cancers in women. It is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. Treatment depends on the tumor stage (stages 1–4) and the characteristics of the tumor cells. These characteristics primarily include the presence of hormone receptors (estrogen- and progesterone-receptor-positive) and/or the HER2 receptor (HER2-positive) on the cells. If these characteristics are absent, the cancer is referred to as triple-negative breast cancer (TNBC). Since this type of cancer cannot be treated with anti-hormone therapies or HER2-targeted therapies, only limited treatment options are currently available. Standard treatment is based primarily on chemotherapy and immunotherapy.

Pembrolizumab is an already approved immunotherapy drug. Pembrolizumab activates the immune system to fight cancer cells. In this study, it is combined with sacituzumab-tirumotecan, a new drug that has not yet been approved in Europe. However, it has a mechanism of action similar to that of sacituzumab-govitecan, which is already approved: It is an antibody-drug conjugate that specifically binds to tumor cells and delivers a cell-killing substance directly into the cancer cell. The combination with pembrolizumab, an immune checkpoint inhibitor, is not currently approved.

The treatment of breast cancer, especially in the early stages, follows standardized protocols: After neoadjuvant therapy (before surgery), the tumor is surgically removed. If residual tumor tissue remains after surgery, the risk of disease recurrence increases. In this case, adjuvant drug therapy (after surgery) may be administered to reduce the risk of recurrence. Radiation therapy may also be necessary.

The goal of the MK-2870-012 study is to investigate new treatment options for patients with triple-negative breast cancer and residual tumor remaining after surgery. To this end, the study will evaluate the efficacy of the combination of sacituzumab-tirumotecan and pembrolizumab compared to individually selected standard therapy. The study is randomized and open-label, which means that patients are randomly assigned to one of the two treatment groups, and both the patients and their treating physicians are aware of the therapy being administered. In one group, patients receive sacituzumab-tirumotecan in combination with pembrolizumab, while the control group receives a therapy selected by the treating medical staff. This may consist of either pembrolizumab alone or a combination of pembrolizumab and capecitabine. Treatment lasts 24 weeks, with pembrolizumab administered as an infusion every six weeks and sacituzumab-tirumotecan given every two weeks. Patients will be monitored regularly for up to 77 months after the start of the study. The primary endpoint of the study is disease-free survival—that is, the time until the disease recurs or the patient dies from breast cancer.

To participate in the study, patients must be at least 18 years old and have triple-negative breast cancer. They must have received neoadjuvant therapy and still have residual tumor in the breast after surgery. Enrollment in the study must occur no later than 12 weeks after surgery. If radiation therapy is necessary, enrollment in the study will take place after that.