Study to Assess the Safety of Alpelisib Plus Fulvestrant, in Men and Post-menopausal Women With HR-positive, HER2-negative, Advanced Breast Cancer (aBC) With PIK3CA Mutation, Whose Disease Progressed on or After Endocrine Treatment

Key Inclusion Criteria:

• Participants with confirmed PIK3CA mutant advanced or metastatic breast cancer

• Postmenopausal females and males ≥ 18 years old with confirmed HR-positive,HER2-negative advanced or metastatic breast cancer.

• Adequate liver function

• Adequate renal function

• Fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4%

• ECOG (Eastern Cooperative Oncology Group) Performance Status < 2

• Fasting Serum amylase ≤ 2 × ULN and Fasting Serum lipase ≤ ULN

• Potassium within normal limits, or corrected with supplements

• Calcium (corrected for serum albumin) and magnesium within normal limits or ≤ grade 1 if judged clinically not significant by the investigator

Key Exclusion Criteria:

• Known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients ofalpelisib or fulvestrant

• Participant ineligible for endocrine therapy per the investigator's judgment

• Participant has received prior treatment with any PI3K inhibitors and / or mTORinhibitor

• Participant with type I diabetes or not controlled type II (based on FPG and HbA1c,see inclusion criterion 6)

• Participant has a concurrent malignancy or malignancy within 3 years of studyscreening period, with the exception of adequately treated, basal or squamous cellcarcinoma, non-melanomatous skin cancer or curatively resected cervical cancer

• Participant has not recovered to grade 1 or better from related side effects ofprior anti cancer therapy (with the exception of alopecia)

• Participants receiving concomitant immunosuppressive agents or chroniccorticosteroids use at the time of study entry except in cases outlined below:Topical applications, inhaled sprays, eye drops or local injections are allowed.Participants on stable low dose of corticosteroids for at least two weeks prior toenrollment are allowed

• Bilateral diffuse lymphangitic carcinomatosis

• Participants with a known history of HIV seropositivity. Screening for HIV infectionat baseline is not required

• Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dosewarfarin and acetylsalicylic acid or equivalent, as long as the INR is ≤2.0)

• Any severe and/ or uncontrolled medical conditions

• Participant with severe liver impairment (Child Pugh score B/C)

• Participant has impairment of gastrointestinal (GI) function or GI disease that maysignificantly alter the absorption of the study drugs

• Participant has any other concurrent severe and/or uncontrolled medical conditionthat would, in the investigator's judgment, contraindicate patient participation inthe clinical study

• Participant has documented pneumonitis/interstitial lung disease which is active andrequiring treatment

• Participant has active cardiac disease or a history of cardiac dysfunction

• Participants with unresolved osteonecrosis of the jaw

• Participant has a history of severe cutaneous reactions likeStevens-Johnson-Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

• Participant is a nursing (lactating) or pregnant woman

• Participant is a woman of child-bearing potential defined as all womenphysiologically capable of becoming pregnant, unless they are using highly effectivemethods of contraception during study treatment and at least for 1 week (foralpelisib) or 1 year (for fulvestrant based on prescribing label) after the lastdose of each study drug (whichever comes later).

• Participant is a sexually active male unwilling to use a condom during intercoursewhile taking study treatment, and for 1 week (for alpelisib) or 1 year (forfulvestrant based on prescribing label) after stopping each study drug (whichevercomes later). A condom is required for all sexually active male participants toprevent them from fathering a child AND to prevent delivery of study treatment viaseminal fluid to their partner. In addition, male participants must not donate spermduring study and up to the time period specified above.