Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments

Inclusion Criteria

• Key Inclusion Criteria: Subjects eligible for inclusion in the Core Phase of the study fulfilled the following key inclusion criteria: - Subject was an adult male or female ≥ 18 years of age. - Subjects with histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive breast cancer by local laboratory. - Subjects with a confirmed human epidermal growth factor receptor-2 (HER2)-negative aBC. - Subjects with gene encoding the p110alpha catalytic subunit of PI3K (phosphatidylinositol-3-kinase) (PIK3CA) mutation. - In case of women, both premenopausal and postmenopausal subjects were allowed to be included in this study. - Subjects with documented evidence of tumor progression on or after: i. Cyclin-Dependent Kinase 4 and 6 inhibitor (CDK4/6i) treatment as last treatment regimen in Cohorts A and B. ii. aromatase inhibitor (AI) treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET (monotherapy or combination except CDK4/6i + AI) as last treatment regimen in Cohort C. Upon completion of enrollment of Cohort B, subjects who received CDK4/6i + fulvestrant as immediate prior therapy were eligible for Cohort C. iii. No more than 2 prior anticancer therapies for aBC. iv. Received no more than 1 prior regimen of chemotherapy for the treatment of advanced/metastatic disease was permitted. v. Recovered to grade 1 or better from any adverse events (AEs) related to previous anticancer therapy prior to study entry (except alopecia or other toxicities not considered a safety risk for the subject at the investigator's discretion). - Subjects with: i. Measurable disease, i.e., at least 1 measurable lesion as per RECIST v1.1 criteria; or ii. If no measurable disease was present, at least 1 predominantly lytic bone lesion had to be present. - Subjects with adequate bone marrow and coagulation function, liver function and renal function as shown by laboratory values. - Subjects with Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2. Key exclusion criteria were: - Subjects with a known hypersensitivity to alpelisib, fulvestrant, letrozole, goserelin, or leuprolide or to any of their excipients. - Subjects with prior treatment with any PI3K inhibitor (PI3Ki). - Subjects with central nervous system (CNS) involvement unless they met all of the following criteria: i. At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment, ii. Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (magnetic resonance imaging (MRI) or computed tomography (CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment. - Subjects with an established diagnosis of diabetes mellitus type I or uncontrolled type II. - Any concurrent severe and/or uncontrolled medical conditions that would, in the investigator's judgment, contraindicate subject participation in the study (e.g., chronic active hepatitis, severe hepatic impairment, etc.). - Subjects with a history of noncompliance to medical regimens. - Subjects with impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of the study drugs based on investigator discretion. - Subjects with documented pneumonitis/interstitial lung disease which was active and requiring treatment. - Subjects concurrently using other anticancer therapy. All anticancer therapy had to be discontinued prior to Day 1 of study treatment. - Subjects who had major surgery within 14 days prior to starting treatment with alpelisib, or did not recover from major side effects. - Subjects with significant cardiac abnormalities. - History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis. - Subjects who did not use highly effective contraception while on alpelisib and through the duration after the final dose of alpelisib (not applicable to postmenopausal women). - Subjects with unresolved osteonecrosis of the jaw. Other inclusion/exclusion criteria may apply