A Study of Imlunestrant in Premenopausal Women with Early-Stage Estrogen Receptor-Positive, HER2-Negative Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast glandular tissue in which cells multiply uncontrollably. Treatment depends on various factors, such as the patient’s overall health and the stage of the tumor, but also on the tumor’s biological characteristics, such as its growth rate (e.g., Ki-67 index), hormone receptor status (estrogen and progesterone receptors), and HER2 status (human epidermal growth factor receptor 2). In premenopausal women, the ovaries continue to produce estrogen, which can promote the growth of hormone receptor-positive cancer cells; therefore, standard treatment often includes anti-hormone therapy, such as tamoxifen. Tamoxifen is a selective estrogen receptor modulator (SERM) that inhibits tumor growth by blocking the binding sites for estrogen in breast tissue. Imlunestrant belongs to the class of selective estrogen receptor downregulators (SERDs), which are designed to promote the breakdown of estrogen receptors on cancer cells and thereby inhibit estrogen-dependent tumor growth. Imlunestrant is taken as a tablet and is already approved for the treatment of advanced estrogen receptor-positive, HER2-negative breast cancer with a specific genetic mutation (ESR1 mutation), but it is not yet approved for use in early-stage breast cancer.

The goal of the Phase 2 study is to investigate the effect of imlunestrant on tumor cells and ovarian function compared to tamoxifen in premenopausal women with early-stage hormone receptor-positive breast cancer. The study comprises two cohorts. In Cohort 1, patients are randomly assigned to three study arms: Study arm A receives imlunestrant alone as a tablet; study arm B receives imlunestrant in combination with goserelin, a synthetic hormone preparation used to suppress ovarian function, which is administered as a subcutaneous injection. Control arm C receives tamoxifen as a tablet. Treatment in Cohort 1 lasts up to 29 days, during which the study will examine how the treatment affects the Ki-67 growth marker in the tumor cells and ovarian function. In Cohort 2, patients are also randomly assigned to two study arms: Study Arm A receives imlunestrant and the control arm B receives tamoxifen, both as tablets for up to six months. This cohort investigates how imlunestrant affects the ovaries and the Ki-67 growth marker in tumor cells without additional suppression of ovarian function. The study is open-label (not blinded), meaning that both the patients and the study physicians know which treatment is being administered.

Eligible participants are premenopausal women aged 18 and older with hormone receptor-positive (ER+), HER2-negative breast cancer. Depending on the study group, eligible participants include either patients with early-stage breast cancer (stages 1–3) prior to planned treatment or patients with early-stage breast cancer who have completed surgery and local treatment. The cancer must not be at an advanced stage (with distant metastases). Another requirement is that the disease exhibits certain biological characteristics (Ki-67 growth marker of at least 10%). For patients in Cohort 2, it is also required that they have already undergone anti-hormonal therapy for at least 2 years.