• Histologically or cytologically confirmed HR+/HER2- metastatic breast cancer. Participants must have received ≥ 2 prior lines of treatment for metastatic disease, including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.

• Female participants will be required (either continue ongoing or initiate as soon as feasible) to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists (such as goserelin) or be postmenopausal.

• Male participants may be required to use GnRH agonists when being treated with fulvestrant at the discretion of the investigator.

• Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.

• Adequate organ function.

• Female participants of childbearing potential and nonsterile male participants with female partners of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study and for 90 days after the last dose of BGB-21447, 3 months after the last dose of BGB-43395, and 2 years after the last dose of fulvestrant.

• Food effect substudy only: Participants who are able and willing to fast overnight (≥ 10 hours) and consume a high-fat meal.