A Study of the New Drug ECI830, Either Alone or in Combination with Ribociclib and Fulvestrant, in Patients with Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease in which cells in the breast glandular tissue multiply uncontrollably. Treatment depends on various factors, including the patient’s overall health, tumor stage, growth rate, and surface characteristics of the cancer cells (such as hormone receptors and HER2 receptors). For hormone receptor-positive, HER2-negative breast cancer, anti-hormone therapy is the standard of care and is often combined with a CDK4/6 inhibitor. Despite these treatment options, the disease continues to progress in some patients, creating a need for new therapeutic approaches. ECI830 is a new drug from the class of CDK2 inhibitors that has not yet been approved for the treatment of cancer. CDK2 is a protein that plays an important role in cell division; inhibiting CDK2 is intended to slow the uncontrolled growth of cancer cells, particularly in tumors that exhibit amplification of the CCNE1 gene (CCNE1 amplification). Ribociclib is a CDK4/6 inhibitor, and fulvestrant is an anti-hormonal agent that blocks the estrogen receptor. Both drugs are already approved for the treatment of advanced hormone receptor-positive breast cancer.

The goal of this Phase 1/2 study is to investigate the optimal dose, safety, and efficacy of the new drug ECI830 as monotherapy and in combination with ribociclib and fulvestrant. To this end, various treatment groups will be evaluated. In the Phase 1 portion, the appropriate dosage of ECI830 will first be determined, both as monotherapy (Study Arm A) and in combination with ribociclib and fulvestrant (Study Arm B). In the Phase 2 portion, patients will be randomly assigned to different groups to compare the efficacy of the combination therapies: ribociclib with fulvestrant (arm C), ECI830 with fulvestrant (study arm D), and ECI830 with ribociclib and fulvestrant (study arms E and F). The study is open-label, meaning that study physicians and patients know which treatment is being administered. The main objective (primary endpoint) in the Phase 2 portion is the proportion of patients whose disease has not progressed after six months.

Women and men aged 18 and older with advanced hormone receptor-positive, HER2-negative breast cancer; other advanced solid tumors with CCNE1 amplification; or extensive-stage small cell lung cancer are eligible to participate in this study. In addition, the breast cancer must have continued to progress (be treatment-refractory) while on prior anti-hormone therapy in combination with a CDK4/6 inhibitor.