BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments

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The study comprised two phases: 1. Core Phase: included a treatment phase for all subjects from first subject first treatment (FSFT) until disease progression, unacceptable toxicity, or death until 18 months post last subject first treatment (LSFT) + 1 month safety follow-up (total 19 months post LSFT), discontinuation from the study treatment for any other reason, or sponsor terminates the study. At the start of the Core Phase, subjects were assigned to Cohort A, Cohort B, or Cohort C based on previous therapy as follows: * Cohort A: alpelisib (300 mg oral QD) + fulvestrant (500 mg intramuscular (IM)) to subjects whose last prior treatment was a CDK4/6i plus any AI; * Cohort B: alpelisib (300 mg oral QD) + letrozole (2.5 mg oral QD) to subjects whose last prior treatment was a CDK4/6i plus fulvestrant; * Cohort C: alpelisib (300 mg oral QD)+ fulvestrant (500 mg IM) to subjects who failed prior AI based therapy and whose last prior treatment was systemic chemotherapy or endocrine therapy (as monotherapy or in combination with targeted treatment except CDK 4/6i + AI). Endocrine therapy included letrozole, fulvestrant and CDK 4/6 inhibitor plus fulvestrant. 2. Extension Phase: included a treatment phase starting at the end of the treatment Core Phase until last subject last visit(LSLV) (up to 36 months). Following the end of the Core Phase, subjects continuing to derive benefit from study treatment who were not eligible for Post-Study Drug Supply (PSDS) in their country based on local regulations were re-consented and transitioned to the Extension Phase. Subjects continued on their existing study treatment assigned in the Core Phase until disease progression/lack of clinical benefit or any other reason for which the subject may have been discontinued from study treatment. If PSDS became available for a subject, the subject was to be discontinued from the study and to access treatment via PSDS. When subjects discontinued treatment for any reason, the end of treatment visit was performed after discontinuation of the medication , followed by safety follow-up 30 days after last dose. A total of 340 subjects were planned to be enrolled, with approximately 112 subjects in each cohort. In the Core Phase, 379 subjects were analyzed, with 127 subjects in Cohort A, 126 subjects in Cohort B, and 126 subjects in Cohort C. In the Extension Phase, 11 subjects were analyzed, with 1 subject in Cohort A and 10 subjects in Cohort C.