BGB-21447 (Bcl-2 Inhibitor) Combinations for Adults With Hormone-Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer

Inclusion Criteria:

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

• Female participants with metastatic breast cancer will be required (either continueongoing or initiate as soon as feasible) to have ovarian function suppression usingGnRH agonists (such as goserelin) or be postmenopausal.

• Male participants will be required to use gonadotropin-releasing hormone (GnRH)agonists when being treated with aromatase inhibitors and can be treated with GnRHagonists 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 withfemale partners of childbearing potential must be willing to use a highly effectivemethod of birth control for the duration of the study and for 90 days after the lastdose of BGB-21447, 3 months after the last dose of BGB-43395, and 2 years after thelast dose of fulvestrant.

Exclusion Criteria:

• Prior Bcl-2 inhibitor exposure.

• Known leptomeningeal disease or uncontrolled, untreated brain metastases.

• Any malignancy ≤ 3 years before the first dose of study treatment(s) except for thespecific cancer under investigation in this study and any locally recurring cancerthat has been treated with curative intent (eg, treated papillary thyroid carcinoma,resected basal or squamous cell skin cancer, superficial bladder cancer, orcarcinoma in situ of the cervix or breast).

• Uncontrolled diabetes.

• History of hepatitis B or active Hepatitis C infection

Note: Other protocol defined Inclusion/Exclusion criteria may apply.