Puma Biotechnology has announced the initiation of the ALISCA™-Breast1, a Phase II clinical trial evaluating the efficacy and safety of alisertib in patients with hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer who have previously progressed on CDK4/6 inhibitor therapy. This multicenter study aims to provide a new treatment option for patients facing resistance to current standard-of-care therapies.
The ALISCA™-Breast1 trial is designed to assess the clinical benefit rate (CBR) of alisertib in this patient population. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and safety. The trial will enroll patients with measurable disease who have experienced disease progression during or after CDK4/6 inhibitor treatment in combination with endocrine therapy.
Rationale for Alisertib
Alisertib is an oral Aurora kinase A inhibitor. Aurora kinases play a crucial role in cell cycle regulation, and their inhibition may disrupt cancer cell proliferation. Preclinical data suggest that alisertib could be effective in overcoming resistance mechanisms developed during CDK4/6 inhibitor therapy. This provides a strong rationale for its evaluation in HR+/HER2- breast cancer patients who have progressed on prior CDK4/6 inhibitor treatment.
Unmet Need in HR+/HER2- Breast Cancer
HR+/HER2- breast cancer is the most common subtype of breast cancer. While CDK4/6 inhibitors have significantly improved outcomes for patients with this disease, resistance inevitably develops, leading to disease progression. There is a significant unmet medical need for effective therapies following CDK4/6 inhibitor failure. The ALISCA™-Breast1 trial seeks to address this need by exploring a novel mechanism of action with alisertib.
Trial Design and Endpoints
The Phase II trial will enroll patients at multiple centers. Patients will receive alisertib orally. The primary endpoint, clinical benefit rate, will be assessed at a pre-specified time point. Secondary endpoints, including PFS, OS, and safety, will provide further insights into the drug's efficacy and tolerability. Detailed inclusion and exclusion criteria are defined to ensure the selection of an appropriate patient population for this study.
