A clinical trial comparing elacestrant and ribociclib to anti-hormonal therapy with ribociclib prior to surgery in patients with hormone receptor-positive, HER2-negative breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue in which cells multiply uncontrollably. Treatment depends, among other factors, on the stage of the disease and the biological characteristics of the tumor. In the early stages of the disease, the goal is usually to surgically remove the tumor. For hormone receptor-positive breast cancer, medications may also be used that inhibit the effects of sex hormones and are intended to slow cancer growth. Such anti-hormone therapy administered before surgery is referred to as neoadjuvant therapy. Elacestrant belongs to the class of selective estrogen receptor degraders (SERDs). The drug binds to the estrogen receptor and specifically degrades it, thereby inhibiting the growth of hormone-dependent cancer cells. Ribociclib is a so-called CDK4/6 inhibitor that blocks key proteins involved in cell division, thereby slowing the growth of cancer cells. Elacestrant is already approved for the treatment of certain forms of advanced or metastatic breast cancer, while ribociclib is approved for the treatment of certain forms of early-stage as well as advanced or metastatic breast cancer. However, their use as neoadjuvant therapy for this treatment scenario is still under investigation. As a standard treatment for early-stage hormone receptor-positive breast cancer, so-called aromatase inhibitors (anastrozole, letrozole, or exemestane) may also be used, which reduce the production of estrogen in the body. Women before or during menopause (pre- or perimenopausal) as well as men receive a GnRH agonist in addition to an aromatase inhibitor; this suppresses the body’s own hormone production.

The goal of this Phase 2 study is to investigate the efficacy of elacestrant in combination with ribociclib compared to an aromatase inhibitor in combination with ribociclib as neoadjuvant therapy prior to surgery. Patients will be randomly assigned to one of two study arms. In the treatment arm, patients will receive elacestrant and ribociclib; in the control arm, they will receive an aromatase inhibitor (plus a GnRH agonist, if applicable) together with ribociclib. After four weeks of treatment, a repeat tissue biopsy will be performed to determine the extent to which the tumor’s cell division activity has decreased (Ki-67). Only if the tumor responds sufficiently to the anti-hormone therapy will treatment continue for an additional five treatment cycles according to the original assignment. Patients whose tumors do not respond sufficiently will discontinue the study treatment and continue treatment outside the study. The study is open-label, meaning that both the patients and the study physicians know which treatment is being administered. The main objective (primary endpoint) of the study is to investigate whether treatment with elacestrant and ribociclib leads to a more favorable modified PEPI score (Preoperative Endocrine Prognostic Index) at the time of surgery. This score is used to estimate the risk of recurrence following neoadjuvant anti-hormonal therapy. The study duration per patient is approximately eight months.

Women and men aged 18 and older with early-stage hormone receptor-positive, HER2-negative breast cancer are eligible to participate. Requirements include, among other things, good overall health and suitability for neoadjuvant anti-hormone therapy. Patients must be willing to provide additional tumor tissue and blood samples for scientific research.