Bylieve: A Phase Ii Study Of Alpelisib (Alp) With Fulvestrant (Ful) Or Letrozole (Let) For Treatment Of Pik3ca Mutant, Hormone Receptor-Positive (Hr Plus ), Human Epidermal Growth Factor Receptor 2-Negative (Her2-) Advanced Breast Cancer (Abc) Progressing On/After Cyclin-Dependent Kinase 4/6 Inhibitor (Cdk4/6i) Therapy.

TPS1107Background: Endocrine therapy (ET) is the standard of care for treatment of HR+, HER2– aBC. However, ET resistance occurs frequently due to dysregulation of the PI3K/AKT/mTOR pathway, specifically mutations in PIK3CA, the gene encoding the p110alpha subunit of PI3K. In a phase 1 study, ALP, a PI3Kα-specific inhibitor, in combination with FUL has shown antitumor activity in patients (pts) with PIK3CA mutant, HR+, HER2– aBC. The ongoing phase 3 SOLAR-1 trial (NCT02437318) is evaluating ALP + FUL combination in HR+, HER2– aBC. The present BYLieve study aims to assess the efficacy and safety of ALP + FUL/LET in PIK3CA-mutant, HR+, HER2– aBC progressing on/after prior CDK4/6i combination therapy. Methods: BYLieve is a phase 2, multicenter, open-label, 2-cohort, non-comparative study. Men and women (pre-menopausal and post-menopausal; ≥18 years) with PIK3CA-mutant, HR+, HER2− locally advanced or metastatic breast cancer that has progressed on/after prior CDK4/6i combination therapy are eligible. Other el...