Novartis has announced the global Phase III SOLAR-1 trial evaluating the investigational alpha-specific PI3K inhibitor BYL719 (alpelisib) has met the primary endpoint showing an improvement in progression-free survival (PFS) in breast cancer patients.
SOLAR-1 is evaluating BYL719 in combination with fulvestrant compared to fulvestrant alone in postmenopausal women and men with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) PIK3CA-mutant advanced or metastatic breast cancer that progressed on or following aromatase inhibitor treatment with or without a CDK4/6 inhibitor.
Currently, there are no approved PI3K inhibitors for HR+ advanced breast cancer. The PI3K pathway plays an important role in regulating cell processes and is the most frequently altered pathway promoting tumour growth, disease progression and treatment resistance in HR+ advanced breast cancer.
Studies have established the role of PI3K signalling in several processes critical for cancer progression, including cell metabolism, growth, survival and motility. Activation of the PI3K pathway in breast cancer is associated with resistance to endocrine therapy, disease progression and poorer prognosis.
Proteins in the PI3K pathway consist of four smaller parts called isoforms. Approximately 40% of HR+ advanced breast cancer patients have genetic mutations that activate the alpha isoform, called PIK3CA mutations. Mutations in the three other isoforms are typically not associated with advanced breast cancer.
BYL719 is an investigational, orally bioavailable, alpha-specific PI3K inhibitor. In breast cancer cell lines harbouring PIK3CA mutations, BYL719 has been shown to potentially inhibit the PI3K pathway and have antiproliferative effects. In addition, cancer cell lines with PIK3CA mutations were more sensitive to BYL719 than those without the mutation across a broad range of different cancers.
The SOLAR-1 trial will continue to assess data for secondary endpoints. Novartis will begin discussions with global health authorities based on these results.
Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development said, “BYL719 is the only alpha-specific PI3K inhibitor and the first one to show potential increased benefit and acceptable tolerability for patients. We are encouraged by the results observed in the SOLAR-1 study and look forward to submitting the data to an upcoming medical congress and starting discussions with health authorities worldwide.”