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