CO40151: This phase I trial is evaluating the safety and effectiveness of an oral drug (Ipatasertib) given in combination with an immunotherapy drug (Atezolizumab) and a chemotherapy drug (either paclitaxel or nab-paclitaxel) in patients with locally advanced or metastatic triple negative breast cancer who have had no prior chemotherapy in the advanced settingA Phase Ib, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Ipatasertib in Combination With Atezolizumab and Paclitaxel or Nab-Paclitaxel in Patients With Locally Advanced or Metastatic Triple-Negative Breast Cancer

Exclusion

General:

• History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
• Active infection requiring antibiotics.
• History of or current evidence of HIV infection.
• Known clinically significant history of liver disease.
• 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 (other than anticipated breast surgery for Cohort 3) during the course of the study.
• Pregnant or breastfeeding.
• New York Heart Association (NYHA) Class II, III, or IV heart failure; left ventricular ejection fraction < 50%; or active ventricular arrhythmia requiring medication.
• Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1.
• Prior treatment with an Akt inhibitor.

Disease-specific:

• For Cohorts 1 and 4: history of or known presence of brain or spinal cord metastases.
• For Cohorts 1 and 4: participants who have received previous systemic therapy for inoperable locally advanced or metastatic TNBC, including chemotherapy, immune checkpoint inhibitors, or targeted agents.
• Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
• Participants who have received palliative radiation treatment 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 and have recovered from all acute, reversible effects.
• Uncontrolled pleural effusion, pericardial effusion, or ascites.
• Uncontrolled tumor related complications.
• Uncontrolled hypercalcaemia or symptomatic hypercalcaemia requiring continued use of bisphosphonate therapy.
• Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1.
• For Cohort 3, participants with the following are excluded: [1] prior history of invasive breast cancer; [2] prior systemic therapy for treatment and/or prevention of invasive breast cancer; [3] previous therapy with anthracyclines or taxanes for any malignancy; [4] bilateral breast cancer; [5] undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes; [6] undergone axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy; [6] history of other malignancy within 5 years prior to screening; [7] history of cerebrovascular accident within 12 months prior to initiation of study treatment; [8] cardiopulmonary dysfunction; [9] known allergy or hypersensitivity to the components of cyclophosphamide/doxorubicin formulations and filgrastim or pegfilgrastim formulations; [10] severe infection within 4 weeks prior to initiation of study treatment; [11] treatment with therapeutic oral or IV (Intravenous) antibiotics within 2 weeks prior to initiation of study treatment and [12] prior treatment with CD137 agonists or immune checkpoint - blockade therapies.

Ipatasertib-specific:

• 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.
• Treatment with strong CYP3A inhibitors or strong CYP3A inducers.

Atezolizumab-specific:

• 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 computed tomography (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 last dose of atezolizumab.
• History of hypersensitivity reactions to study drug or any component of the study drug formulation.
• Treatment with systemic immunostimulatory agents and immunosuppressive medication treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.

Paclitaxel-specific:

- Grade >= 2 peripheral neuropathy.