Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) represents approximately 15% of all breast cancers (BC) worldwide. The term triple negative means that tumor growth is not stimulated by the hormones estrogen and progesterone, nor by the HER2 protein, so unlike other types of BC, TNBC, which is an aggressive form of BC, does not have specific effective therapies available being the least common form of BC and the most difficult to treat. Advanced or metastatic TNBC is treated with combinations of platinum-based chemotherapy with taxanes or gemcitabine with a 5-year survival rate of 12%. Recent studies have shown that TNBC expresses Interleukin 1 Receptor Accessory Protein (IL1RAP) at higher levels than other forms of BC. Nadunolimab is a fully humanized monoclonal antibody that blocks the signals that occur within the cell produced by IL1RAP protein, thereby impairing the cancer cells' ability to secrete tumor stimulating substances, in turn reducing the tumor, inflammation and tumor progression. On the other hand, it is an antibody designed to activate the immune system to fight cancer cells. This clinical trial is divided into two phases, phase Ib in which it is expected to include up to 15 patients and phase II in which it is expected to include 102 patients. The main purpose of phase Ib is to ensure that the combination of nadunolimab plus chemotherapy (gemcitabine plus carboplatin) is safe and determine the highest dose of nadunolimab that can be given safely without causing serious side effects. If the pre-specified objectives in this part are achieved, the trial will be expanded to a randomized phase II, to evaluate the efficacy of the combination of nadunolimab plus gemcitabine plus carboplatin, compared to a control group that will receive gemcitabine plus carboplatin only.