A Study of Ipatasertib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Hormone Receptor Positive and HER2 Negative Locally Advanced Unresectable or Metastatic Breast Cancer

Inclusion Criteria

• HR+ HER2- adenocarcinoma of the breast that is locally advanced unresectable or metastatic
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm
• Radiologic/objective relapse during adjuvant endocrine therapy or disease progression during the initial 12 months of 1L endocrine therapy in locally advanced unresectable or metastatic breast cancer
• At least one measurable lesion via Response Evaluation Criteria in Solid Tumors, Version 1.1
• Phase III only: Tumor specimen from the most recently collected, available tumor tissue

Exclusion Criteria

• Pregnant or breastfeeding, or intending to become pregnant
• Prior treatment with fulvestrant or other selective estrogen receptor down-regulator
• Prior treatment with PI3K inhibitor, mTOR inhibitor or AKT inhibitor
• Phase III only: Prior treatment with CDK4/6 inhibitor for locally advanced unresectable or metastatic breast cancer
• Prior treatment with a cytotoxic chemotherapy regimen for metastatic breast cancer
• History of Type I or Type II diabetes mellitus requiring insulin
• History of or active inflammatory bowel disease or active bowel inflammation
• Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections