Study of a New Targeted Therapy Using the Active Ingredient RLY-2608 for Hormone Receptor-Positive, HER2-Negative Breast Cancer with a PIK3CA Mutation

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue in which the cells of the breast gland multiply uncontrollably. Treatment depends on numerous factors, such as the patient’s overall health, the stage of the disease, the HER2 receptor status on the surface of the cancer cells, and other biological characteristics of the cancer cells. In hormone receptor-positive breast cancer, the cancer cells respond to the body’s own hormones, such as estrogen, by growing; therefore, antihormonal therapy is used to inhibit this growth. In addition, CDK4/6 inhibitors (medications that block certain enzymes involved in cell division) are often combined with anti-hormone therapy to enhance its effectiveness. If the disease continues to progress under this therapy, new treatment options are required. Patients with hormone receptor-positive breast cancer may also have what is known as a PIK3CA mutation. This is a genetic change in the cancer cells that permanently activates a specific signaling pathway (the PI3K signaling pathway), thereby promoting tumor growth. RLY-2608 (zovegalisib) is a novel drug that specifically inhibits the altered form of the PI3K enzyme, while the normal form remains largely unaffected. The drug is taken as a tablet and has not yet been approved for the treatment of this disease. Capivasertib is an AKT inhibitor that is also taken as a tablet and acts at a different point in the same signaling pathway. Both drugs are administered in combination with fulvestrant, an anti-hormonal therapy drug that is given as an intramuscular injection.

The goal of this Phase 3 study is to investigate the efficacy and safety of the new active ingredient RLY-2608 in combination with fulvestrant compared to capivasertib in combination with fulvestrant. Patients will be randomly assigned to two treatment groups: In the study arm, patients will receive RLY-2608 together with fulvestrant; in the control arm, they will receive capivasertib together with fulvestrant. 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 progression-free survival (PFS), defined as the time without disease progression, for up to 77 months.

Women and men aged 18 and older with hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer in which a PIK3CA mutation has been detected are eligible to participate in this study. In addition, the disease must have progressed during or after treatment with a CDK4/6 inhibitor, and patients may have received no more than two lines of anti-hormone therapy and one line of a CDK4/6 inhibitor previously.