A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

Inclusion Criteria:

• Women or men aged =>18 years with histologically documented triple-negative breastcancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced ormetastatic and is not amenable to resection with curative intent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate hematologic and organ function within 14 days prior to treatment initiation
• Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that islocally advanced or metastatic and is not amenable to resection with curative intent
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)v1.1
• Eligible for taxane monotherapy, as per local investigator assessment (e.g., absenceof rapid clinical progression, life-threatening visceral metastases, or the need forrapid symptom and/or disease control which may require combination chemotherapy)
• HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapyand meets one of the following: patient has recurrent disease <=5 years of being onadjuvant endocrine therapy or if patient with de novo metastatic disease haveprogressed within 6 months of being on first line endocrine therapy.
• Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block orfreshly cut unstained, serial tumor slides from the most recently collected tumortissue for central molecular analysis
• Confirmation of biomarker eligibility using an appropriately validated molecular assayat a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) orequivalently accredited i.e., valid results from either central testing or localtesting of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status
• For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraception and agreement to refrain from donatingeggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or usecontraceptive methods and agreement to refrain from donating sperm

Exclusion Criteria:

• Treatment with approved or investigational cancer therapy within 14 days prior totreatment initiation
• Any previous chemotherapy for inoperable locally advanced or metastatic TNBC orHR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapyeligible provided they have at least a 12 month disease-free interval)
• History of or known presence of brain or spinal cord metastases
• Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skincarcinoma, or Stage I uterine cancer)
• Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
• History of malabsorption syndrome or other condition that would interfere with enteralabsorption or results in the inability or unwillingness to swallow pills
• Active infection requiring systemic anti-microbial treatment (including antibiotics,anti-fungals, and anti-viral agents)
• Known human immunodeficiency virus (HIV) infection
• Known clinically significant history of liver disease consistent with Child-Pugh ClassB or C, including active viral or other hepatitis, current drug or alcohol abuse, orcirrhosis
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 daysprior to initiation of treatment (or anticipated need during study)
• Pregnant or breastfeeding, or intending to become pregnant during the study
• Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heartfailure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmiarequiring medication, history of myocardial infarction within 6 months of treatmentinitiation, clinically significant electrocardiogram [ECG] abnormalities).
• Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or anequivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for achronic disease
• Unresolved, clinically significant toxicity from prior therapy, except for alopeciaand Grade 1 peripheral neuropathy
• Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, orascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiringcontinued use of bisphosphonate therapy)
• History of Type I or Type II diabetes mellitus requiring insulin
• Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
• History of or active inflammatory bowel disease or active bowel inflammation
• Clinically significant lung disease (including pneumonitis, interstitial lung disease,idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history ofopportunistic infections)
• Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5drug-elimination half-lives, whichever is longer, prior to initiation of treatment
• Grade >=2 peripheral neuropathy