A Study of a Combination of Targeted Radiation Therapy and Chemotherapy (Capecitabine) in Patients with Advanced, Hormone Receptor-Positive, HER2-Negative Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. If the disease is already advanced (extensive spread within the breast and/or metastases), a cure may no longer be possible. It is precisely for this situation that new drugs are constantly being researched to offer patients additional treatment options. One specific type of drug therapy involves the use of radioactive substances that can bind to cancer cells and then destroy them through radiation. Such therapies are already available for various other types of cancer; however, there are currently few such treatment approaches for breast cancer. [177Lu]Lu-NeoB is a new substance that recognizes a specific receptor on cells (known as GRPR). Since breast cancer cells may also have this receptor on their surface, this therapy can be used in such cases. At the start of the study, an imaging examination (PET/CT or PET/MRI) is performed using the contrast agent [68Ga]Ga-NeoB to ensure that the tumor actually has GRPR receptors; radioligand therapy is effective only if this is the case.

Capecitabine is a drug that is converted into its active ingredient only once it reaches the tumor tissue. There, it blocks cell division in the malignant cells. As a result, the tumor cells cannot continue to multiply and die off. Because the active ingredient is activated specifically in tumor cells, the treatment is often more targeted and better tolerated than conventional chemotherapy. This drug is already approved.

The goal of the NeoB-Cap1 study is to investigate whether a combination therapy of [177Lu]Lu-NeoB and the chemotherapeutic agent capecitabine can represent a new treatment option for advanced breast cancer. The study will be conducted in two phases. In Phase 1, the optimal dosage for the combination therapy will be determined. There are four groups with different dosages of the radioactive therapy, into which patients will be randomly assigned. In Phase 2, the study will assess how effective the therapy is against the tumor. The actual treatment with [¹⁷⁷Lu]Lu-NeoB is administered either every 3 weeks (Q3W) or every 6 weeks (Q6W), depending on the dosage group. Depending on the regimen, patients receive either 6 cycles (Q6W) or 12 cycles (Q3W) of radioligand therapy, each in combination with capecitabine for 14 days per cycle. The total treatment duration is therefore approximately 4 to 9 months, depending on the regimen—with regular follow-up visits approximately every 3 weeks during the first 9 months and every 6 weeks thereafter. The study duration, including follow-up, is up to 5 years.

Adults with advanced, hormone receptor-positive, HER2-negative breast cancer who have previously received therapy with CDK4/6 inhibitors and whose disease has progressed are eligible to participate in the study. One of the requirements is that the tumor express certain receptors (GRPR), which are detected via specialized imaging. If a BRCA1 or BRCA2 mutation is present, prior treatment with a PARP inhibitor is also permitted. For so-called HER2-low tumors (low number of HER2 receptors), prior treatment with trastuzumab deruxtecan (Enhertu®) is also possible. Participants must not have received prior treatment with capecitabine or other radiopharmaceuticals and must be in good general health with stable organ function. Excluded are, among others, individuals with inflammatory breast cancer, untreated or unstable brain metastases, severe heart problems, or gastrointestinal disorders that interfere with medication absorption. Previous radiation therapy to more than 25% of the bone marrow or participation in another study within the last 30 days also disqualifies a participant. Women of childbearing age must use reliable methods of contraception or be verifiably infertile.