Study of Capivasertib in Combination with Anti-Hormonal Therapy for Advanced Breast Cancer

Breast cancer (mammary carcinoma) is a malignant disease in which cells in the breast tissue multiply uncontrollably. Treatment of the disease depends on numerous factors, such as the patient’s general health, the stage of the disease, the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of HER2 receptors on the cells (HER2-positive). If the cancer is locally advanced or has already spread to other parts of the body (metastasized), the goal of treatment is often to keep the disease under control for as long as possible. Hormone receptor-positive breast cancer is usually treated with anti-hormone therapy, such as fulvestrant. In some patients, the tumor cells exhibit specific genetic alterations in the so-called PI3K/AKT/PTEN signaling pathway, which normally plays an important role in tumor cell growth. Capivasertib is an approved AKT inhibitor that specifically blocks this signaling pathway in tumor cells and is thus intended to inhibit their growth.

The goal of this Phase 3 study is to evaluate capivasertib in combination with anti-hormone therapy using fulvestrant. The primary objective is to determine how long patients benefit from treatment with capivasertib before the next therapy becomes necessary (Time to Next Treatment, TTNT). This study does not have an active control arm; data from the earlier CAPItello-291 study, in which patients received fulvestrant along with a placebo, will serve as a comparison. In addition, the study will investigate whether continuous digital support (the CANKADO app), which includes symptom tracking and quality-of-life questionnaires, provides a positive benefit for patients. The study is open-label, meaning that both patients and study physicians know which medication is being administered. In the study, all patients receive the active ingredient capivasertib in combination with anti-hormonal therapy. Capivasertib is taken as a tablet for four consecutive days, followed by a three-day treatment break. This dosing schedule is repeated continuously throughout the treatment. In addition, patients receive fulvestrant, an anti-hormonal therapy administered as an intramuscular injection once every 28 days. In premenopausal women, a so-called GnRH agonist is also used. This treatment aims to suppress hormone production in the ovaries and, consequently, estrogen production, which promotes tumor growth. The study includes a 2-year recruitment phase, followed by a treatment and follow-up phase lasting up to 5 years. The actual duration of the study for individual patients depends on the date of enrollment.

Women and men aged 18 and older with hormone receptor-positive, HER2-negative, locally advanced, or metastatic breast cancer are eligible to participate in the study. The disease must have progressed during prior anti-hormone therapy or have recurred within twelve months of the end of that therapy. In addition, specific genetic alterations in the PI3K/AKT/PTEN signaling pathway (PIK3CA, AKT1, or PTEN alterations) must be detectable in the tumor. Premenopausal women must be willing to receive additional anti-hormone therapy with a GnRH agonist.