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

Eligibility Criteria

• * Histologically or cytologically confirmed HR+/HER2- metastatic breast cancer. Participants must have received at least 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 with metastatic breast cancer will be required (either continue ongoing or initiate as soon as feasible) to have ovarian function suppression using GnRH 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 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.
• * 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 the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, treated papillary thyroid carcinoma, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
• * Uncontrolled diabetes.
• * History of hepatitis B or active Hepatitis C infection