A Study Of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer.

Inclusion Criteria:

Willingness and ability to complete all study-related assessments, including PRO assessments, in the investigator's judgement.
Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1.
Life expectancy of at least 6 months.
Measurable disease according to RECIST v1.1.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.
Appropriate candidate for paclitaxel monotherapy if tumor PD-L1 status is unknown or non-positive; appropriate candidate for paclitaxel and atezolizumab if tumor PD-L1 status is positive.
Histologically documented triple-negative adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent.

Exclusion Criteria:

Inability to comply with study and follow-up procedures.
History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
Severe infection within 4 weeks prior to initiation of study treatment (including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia) as well as those who have received treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment.
Known HIV infection (there must be a negative HIV test at screening).
Known clinically significant history of liver disease consistent with Child-Pugh Class B or C.
Current treatment with anti-viral therapy for HBV.
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the study.
Pregnancy or breastfeeding, or intention to become pregnant during the study or within 28 days after the final dose of ipatasertib/placebo, 5 months after the final dose of atezolizumab/placebo, and 6 months after the final dose of paclitaxel whichever occurs later.
New York Heart Association Class II, III, or IV heart failure, left ventricular ejection fraction < 50%, or active ventricular arrhythmia requiring medication.
Current unstable angina or history of myocardial infarction within 6 months prior to Day 1 of Cycle 1.
Congenital long QT syndrome or screening QT interval corrected through use Fridericia's formula (QTcF) > 480 ms.
Current treatment with medications used at doses known to cause clinically relevant prolongation of QT/QTc interval.
History or presence of an abnormal ECG that is clinically significant in the investigator's opinion (including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction).
Requirement for chronic corticosteroid therapy of > 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents for a chronic disease.
Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1.
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high risk from treatment complications.
History of or known presence of spinal cord metastases, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments.
Known CNS disease, except for treated asymptomatic CNS metastases.
Known germline BRCA1/2 deleterious mutation, unless the participant is not an appropriate candidate for a PARP-inhibitor.
Any previous systemic therapy for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast.
Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
Participants who have received palliative radiotherapy to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute, reversible effects (e.g., to Grade 1 or resolved by enrolment).
Uncontrolled pleural effusion, pericardial effusion or ascites.
Uncontrolled tumor-related pain.
Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer.
Known hypersensitivity or contraindication to any component of the study treatments, including the paclitaxel excipient, macrogolglycerol ricinoleate.
Grade >= 2 peripheral neuropathy.
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 (e.g., Crohn disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia).
Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug.
Prior treatment with an Akt inhibitor.
Active or history of autoimmune disease or immune deficiency.
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
Prior allogeneic stem cell or solid organ transplantation.
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with atezolizumab or within 5 months after the final dose of atezolizumab.
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies.
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
Treatment with systemic immunosuppressive medication (including, but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study.