A Study of the Combination of Elacestrant and Everolimus in Patients with Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer with an ESR1 Mutation Following Prior Treatment with Anti-Hormonal Therapy and a CDK4/6 Inhibitor

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue characterized by the uncontrolled proliferation of breast gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage of the disease, the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor- or progesterone receptor-positive) and the increased presence of the HER2 receptor on the cells (HER2-positive). In locally advanced or metastatic stages, the disease is often no longer curable, and the goal is to slow its progression for as long as possible. Hormone receptor-positive breast cancer is typically treated with anti-hormone therapy, which is often combined with a CDK4/6 inhibitor. CDK4/6 inhibitors inhibit the division of cancer cells by blocking the cell cycle. However, as the disease progresses, a change in the estrogen receptor gene (ESR1 mutation) may develop, causing certain anti-hormone therapies to become less effective. Elacestrant is a selective estrogen receptor degrader (SERD) that specifically degrades the estrogen receptor, thereby inhibiting estrogen-dependent tumor growth. Elacestrant is already approved as monotherapy for postmenopausal women and men with advanced hormone receptor-positive, HER2-negative breast cancer with an ESR1 mutation following prior anti-hormonal therapy and is taken as a tablet. Everolimus is an mTOR inhibitor that blocks an important signaling pathway involved in cancer cell growth and survival. This can slow tumor growth. Everolimus is also already approved for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer and is taken as a tablet.

The goal of this Phase 3 study is to investigate the efficacy of the combination of elacestrant and everolimus compared to elacestrant alone. Patients will be randomly assigned to two groups. In the treatment arm, patients will receive elacestrant together with everolimus daily as a tablet. In the control arm, patients will receive elacestrant together with a placebo. The study is double-blind, meaning that neither the patients nor the study physicians know whether everolimus or the placebo is being administered. Treatment will continue in 28-day cycles as long as the disease does not progress and the treatment is well tolerated. After treatment ends, regular follow-up examinations will be conducted. The study’s follow-up period will last up to twelve months after the last patients are enrolled in the study.

Women and men aged 18 and older with advanced or metastatic, hormone receptor-positive, HER2-negative breast cancer and an ESR1 mutation, in whom the disease has continued to progress while on anti-hormone therapy with a CDK4/6 inhibitor, are eligible to participate in this study.