The new drug Datopotamab-Deruxtecan, with or without Durvalumab, compared to standard chemotherapy in patients with PD-L1-positive, advanced triple-negative 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, among other factors, on the stage of the cancer, the patient’s overall health, and the tumor’s biological characteristics. In triple-negative breast cancer (TNBC), the tumor cells lack both hormone receptors (estrogen and progesterone receptors) and the HER2 receptor, which is why neither hormone therapy nor HER2-targeted therapy is effective. In the locally advanced or metastatic stage, a cure is generally no longer possible, so the goal of treatment is to control the disease for as long as possible and maintain quality of life. For patients whose tumor cells express sufficient amounts of the PD-L1 biomarker (PD-L1-positive), chemotherapy in combination with the immunotherapy drug pembrolizumab is currently used as first-line treatment. Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate that is being tested in this study for the treatment of this disease. It consists of an antibody that specifically binds to the TROP2 protein on the surface of tumor cells, and a chemotherapy agent coupled to it, which is thus delivered specifically into the cancer cells. Durvalumab is another immunotherapy designed to support the body’s own defense against cancer cells.

In this open-label Phase 3 study, patients are randomly assigned to one of three study arms. In the first study arm, Dato-DXd is administered in combination with durvalumab as an intravenous infusion. In the control arm, patients receive standard chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine in combination with carboplatin) along with pembrolizumab, also as an intravenous infusion. In a third study arm, Dato-DXd is administered as monotherapy. The primary objective of the study is to determine whether treatment with Dato-DXd and durvalumab helps keep the disease from progressing for a longer period (progression-free survival) compared with standard chemotherapy and pembrolizumab. In addition, the study aims to investigate whether the treatment can prolong overall survival.

Patients aged 18 and older with PD-L1-positive, locally recurrent, inoperable, or metastatic triple-negative breast cancer are eligible to participate in this study. They must also be in good general health and must not have previously received chemotherapy or other drug-based cancer therapy for the inoperable or metastatic stage of the disease.