Comparison of the Active Substance RO7771950 with Tucatinib in Combination with Trastuzumab and Capecitabine in Pre-treated HER2-Positive Breast Cancer

HER2-positive breast cancer is a form of breast cancer in which the tumor cells express elevated levels of the HER2 receptor on their surface, which can promote the growth of cancer cells. In advanced disease, the tumor can also spread to the central nervous system (CNS) and form metastases there, such as in the brain (brain metastases) or in the meninges (leptomeningeal metastases). RO7771950 is an investigational drug that has not yet been approved; it was developed to cross the blood-brain barrier and thereby reach tumor cells in the central nervous system. This is the natural barrier that protects the central nervous system and makes it difficult for many drugs to enter the brain. RO7771950 is a so-called tyrosine kinase inhibitor; it is administered as a tablet (orally) and is being compared to tucatinib, an already approved tyrosine kinase inhibitor. Tyrosine kinase inhibitors block signal transmission via the HER2 receptor, leading to the death of tumor cells. Both drugs are administered in combination with trastuzumab, a monoclonal antibody that targets the HER2 receptor (administered as an intravenous infusion or a subcutaneous injection), and the chemotherapy drug capecitabine.

The goal of this Phase 2/3 study is to compare the new drug RO7771950 with the drug tucatinib, each in combination with trastuzumab and capecitabine. Patients will be randomly assigned to three treatment groups (randomized). There are two study arms in which RO7771950 is administered twice daily as a tablet at different doses, as well as a control arm with tucatinib, each in combination with trastuzumab and capecitabine. The study is open-label (not blinded), 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 for up to 35 months—that is, the time during which the tumor does not grow, no new metastases develop, and the disease does not progress.

Eligible participants include women and men aged 18 and older with locally advanced, inoperable, or metastatic HER2-positive breast cancer. The disease must have previously been treated with at least one therapy targeting the HER2 receptor, which typically includes an antibody-drug conjugate. Prior treatment with a tyrosine kinase inhibitor is permitted only if it was administered as part of (neo)adjuvant therapy and was completed more than twelve months before the onset of advanced disease. No tyrosine kinase inhibitor may have been used previously to treat the advanced or metastatic disease. Patients with central nervous system metastases—whether previously treated or still untreated—are also eligible to participate.