Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant in Participants With HR-positive (HR+), HER2-negative, Advanced Breast Cancer After Treatment With a CDK4/6 Inhibitor and an Aromatase Inhibitor.

Key Inclusion Criteria:

• Participant is an adult ≥ 18 years old at the time of informed consent and hassigned informed consent before any trial related activities and according to localguidelines.

• Participant has a histologically and/or cytologically confirmed diagnosis of ER+and/or PgR+ breast cancer by local laboratory.

• Participant has HER2-negative breast cancer defined as a negative in situhybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situhybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situhybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test isrequired by local laboratory testing.

• Participant has at least one measurable lesion as per RECIST v1.1 criteria asassessed by Investigator (a lesion at a previously irradiated site may only becounted as a target lesion if there is clear sign of progression since theirradiation).

• Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combinedAI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).

• Participant has received ≤ 2 prior lines of systemic therapies overall in themetastatic setting, of which a maximum of 1 line of prior treatment withchemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted.

• The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollmenteither by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by alocal laboratory using a Food and Drug Administration (FDA)-approved PIK3CACompanion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen®PIK3CA RGQ PCR test.

• If female, then the participant must be in postmenopausal status.

Key Exclusion Criteria:

• Participant with symptomatic visceral disease or any disease burden that makes theparticipant ineligible for endocrine therapy (ET) per the Investigator's bestjudgment.

• Participant who relapsed with documented evidence of progression more than 12 monthsfrom completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatmentfor metastatic disease.

• Participant has received prior treatment with fulvestrant, any oral selectiveestrogen receptor degrader (SERD), any Phosphatidylinositol-3-Kinase (PI3K),mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor.

Other Inclusion and Exclusion Criteria do apply