A Study of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as Initial Treatment for Participants With Triple-Negative Breast Cancer That Has Spread

Inclusion Criteria:

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Histologically confirmed estrogen receptor (ER)-negative, progesterone receptor
(PR)-negative, and human epidermal growth factor 2 (HER2)-negative adenocarcinoma of
the breast with measurable metastatic or locally advanced disease

- Locally advanced disease must not be amenable to resection with curative intent

- Measurable disease, according to RECIST, v1.1

- Adequate hematologic and end organ function

- Agreement to use highly effective contraceptive methods as stated in protocol

Exclusion Criteria:

Disease-Specific Exclusion Criteria

- Known HER2-, ER-positive, or PR-positive breast cancer by local laboratory assessment

- Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced
or metastatic triple-negative breast cancer (mTNBC)

- Any systemic anticancer therapy within 3 weeks prior to Cycle 1, Day 1

- Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1

- Major surgical procedure, open biopsy, or significant traumatic injury within 30 days
prior to Cycle 1, Day 1 or anticipation of need for major surgical procedure during
the course of the study

- Prior exposure to experimental treatment targeting rapidly accelerated fibrosarcoma
(Raf), MAP kinase/ERK kinase (MEK), or the mitogen-activated protein kinase (MAPK)
pathway

- Brain metastases (symptomatic or nonsymptomatic) that have not been treated
previously, are progressive, or require any type of therapy (e.g., radiation, surgery,
or steroids) to control symptoms from brain metastases within 30 days prior to first
study treatment dose

Cobimetinib-Specific Exclusion Criteria

- History of or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment/central serous
chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular
degeneration

- Cobimetinib is metabolized by the hepatic cytochrome P3A4 (CYP3A4) enzyme. Drugs
CYP3A4/5 inhibitors and inducers should be avoided

Atezolizumab-Specific Exclusion Criteria (Cohorts II and III Only)

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any component of the atezolizumab formulation

- History of autoimmune disease

- Prior allogenic stem cell or solid organ transplantation

- History of idiopathic pulmonary fibrosis (including pneumonitis), drug induced
pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic
organizing pneumonia), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan

- Positive test for Human Immunodeficiency Virus (HIV)

- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg]
or positive hepatitis B virus [HBV] deoxyribonucleic acid [DNA] test at screening) or
hepatitis C

- Active tuberculosis

- Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or
anticipation that such a live, attenuated vaccine will be required during the study

- Prior treatment with cluster of differentiation (CD) 137 (CD137) agonists or immune
checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated
protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-programmed death
ligand-1 (anti-PD-L1) therapeutic antibodies

- Treatment with systemic immunostimulatory agents (including but not limited to
interferons or Interlukin-2 [IL-2]) within 4 weeks or five half-lives of the drug
(whichever is shorter) prior to randomization

- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications within 2 weeks prior to randomization, or anticipated requirement for
systemic immunosuppressive medications during the trial

Cardiac Exclusion Criteria

- History of clinically significant cardiac dysfunction

- Corrected QT interval at screening greater than (>) 480 milliseconds (ms) (average of
triplicate screening measurements)

- Left ventricular ejection fraction (LVEF) below the institutional lower limit of
normal or below 50 percent (%), whichever is lower

General Exclusion Criteria

- No other history of or ongoing malignancy that would potentially interfere with the
interpretation of the pharmacodynamic or efficacy assay

- Pregnancy (positive serum pregnancy test) or lactation

- Uncontrolled serious medical or psychiatric illness

- Active infection requiring IV antibiotics on Cycle 1, Day 1

- Participants who have a history of hypersensitivity reactions to paclitaxel or other
drugs formulated in Cremophor® EL (polyoxyethylated castor oil) or to nab-paclitaxel
and any of the excipients