Camizestrant in combination with ribociclib for advanced, hormone receptor-positive breast cancer

Breast cancer develops when cells in the glandular tissue of the breast become abnormal and multiply uncontrollably. As the disease progresses, cancer cells can spread and form secondary tumors (metastases) in lymph nodes or other organs. In the hormone receptor (HR)-positive form, the tumor cells have binding sites (receptors) for the female sex hormones estrogen and progesterone. When estrogen binds to these hormone receptors, it can trigger signals that stimulate the cancer cells to divide, thereby promoting tumor growth. The human epidermal growth factor receptor 2 (HER2) is also a receptor on the surface of cancer cells, though it binds to different growth factors. HER2-negative means that it is not present in elevated levels on the tumor cells. At the same time, the presence of hormone receptors also provides targets for targeted therapies. In hormone receptor-positive, HER2-negative breast cancer, anti-hormone therapy therefore generally forms the basis of treatment. Various medications are available that block the hormone receptors (selective estrogen receptor modulators, SERMs) or degrade them (selective estrogen receptor degraders, SERDs) or suppress hormone production (aromatase inhibitors). Tumor cells can become resistant to these treatments over time, allowing the disease to progress. In modern cancer therapy, therefore, multiple active ingredients that act at different targets are often combined to combat the tumor more comprehensively. In this study, two drugs are combined that target the tumor at different sites. Camizestrant belongs to the class of selective estrogen receptor degraders (SERDs), while ribociclib belongs to the class of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors). Ribociclib specifically blocks these enzymes, which drive cell division, and is thus intended to halt the cell cycle of cancer cells and prevent uncontrolled cell division.

The goal of this Phase 2 study is to investigate the efficacy and tolerability of the combination of camizestrant and ribociclib in patients with advanced hormone receptor-positive and HER2-negative breast cancer. Both study medications are taken in tablet form in 28-day cycles: camizestrant every day of the cycle and ribociclib for the first 21 days of each cycle. All patients receive the same treatment; therefore, assignment is not random (non-randomized), and there is no comparison group (non-controlled). Instead, data from previous clinical trials are used for comparison (historical control arm). The study is open-label, meaning it is not blinded. This means that both the patients and the study physicians know which medications are being taken. The primary endpoint is the length of time the disease does not progress while patients are on the combination therapy (progression-free survival, PFS). Safety and tolerability are also being assessed. The follow-up period for individual patients is up to 28 months.

Eligible participants are patients aged 18 and older with hormone receptor-positive and HER2-negative breast cancer that has recurred locally (recurrence) and is inoperable or has already metastasized. Additional requirements include at least five years of anti-hormone therapy, including at least two years with an aromatase inhibitor, as well as disease progression during or after treatment. Patients whose advanced disease has already been treated systemically or who have previously received a medication from the class of estrogen receptor downregulators (SERDs) are not eligible to participate.