Today, breast cancer is the most frequently diagnosed malignancy among women worldwide. This heterogeneous disease is characterized by the presence of different subtypes and multiple clinical outcomes, mostly depending on the molecular characterization and stage. Luminal breast cancers are tumors depending on hormone-receptor overexpression (HR+), with lack of HER2 amplification (HER2-), which can be properly controlled at early stages with endocrine therapy (ET). However, after cycles of ETs, many patients stop responding and progress to an advanced metastatic stage. When this happens, there are no well-defined therapeutic alternatives, being chemotherapy the clinical standard for those patients.
For this purpose, MEDSIR, in collaboration with Cellestia, designed the project CAILA. This is a Phase II, multicenter, single arm clinical trial that will evaluate safety and efficacy of CB-103 administration to HR+/HER2- advanced breast cancer patients, who previously received ET. In this trial, MEDSIR will evaluate safety and efficacy of CB-103, a first in class inhibitor, designed to specifically inhibit Notch signaling, combined with anastrozole or letrozole (ET), with the final goal to introduce a new therapeutic alternative for this class of advanced luminal breast cancer patients.
"Endocrine therapy is the standard of care for luminal breast cancer patients. This treatment blocks or reduces the activity of female sex hormones (estrogen and progesterone), responsible for the growth of breast cancer cells. However, after initial response to ET, these patients often end up developing resistance, which means that the tumor finds new ways to continue its growth", explained Javier Cortés, oncologist and head of the Breast and Gynecological Cancer Unit of the Quirón Group Breast Cancer Institute, and the scientific director of the CAILA trial.
In fact, recent studies indicate that although hormonal blockade by ET hampers tumor growth, at the same time this can induce an overactivation of Notch signaling, an oncogenic pathway involved in numerous malignancies, stimulating cancer cells to growth. It is estimated that this pathway plays an essential role in 40-50% of HR+ breast cancers, meaning that in these tumors Notch inhibition will likely help to control tumor progression.
CB-103 showed high efficacy and tolerability in preclinical studies, using advanced luminal breast cancer models, and further demonstrated increased antitumor activity when combined with ET in ET-resistant breast cancer cells. Preliminary data from an ongoing phase I/IIa clinical study indicate that CB-103 is safe and tolerable in cancer patients, exploring its administration for patients with advanced breast cancer who received previous treatments with ET.
From MEDSIR, we hope that the success of this trial will lead to the introduction of a new therapeutic approach other than chemotherapy for all those patients who developed resistance to ET-based treatments, contributing to enlarge the range of therapeutic possibilities available.
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