A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer

Inclusion Criteria:

- Histologically confirmed triple negative breast cancer(TNBC) that is either locally
recurrent, inoperable and cannot be treated with curative intent or is metastatic

- Documented disease progression occurring within 12 months from the last treatment with
curative intent

- Have not received prior chemotherapy or targeted systemic therapy for their locally
advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent
disease is permitted

- Measurable or non-measurable disease, as defined by RECIST 1.1

- Availability of a representative formalin-fixed paraffin-embedded (FFPE) tumour block
(preferred) or at least 25 unstained slides with an associated pathology report, if
available

- Eastern Cooperative Oncology Group performance status 0-1

- Life expectancy ≥ 12 weeks

- Adequate haematologic and end-organ function

- Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface
antigen (HBsAg) test at screening

- Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb
test followed by a negative hepatitis B virus (HBV) DNA test at screening

- The HBV DNA test will be performed only for patients who have a positive HBcAb test

- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody
test followed by a negative HCV RNA test at screening.

- Women of childbearing potential must agree to remain abstinent (refrain from
heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per
year during the treatment period and for at least 5 months after the last dose of
study treatment

- Men must agree to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agree to refrain from donating sperm

Exclusion Criteria:

- Spinal cord compression not definitively treated with surgery and/or radiation, or
previously diagnosed and treated spinal cord compression without evidence that disease
has been clinically stable for > 2 weeks prior to randomisation

- Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.

- Symptomatic or rapid visceral progression

- No prior treatment with an anthracycline and taxane

- History of leptomeningeal disease

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently) (patients with indwelling
catheters such as PleurX® are allowed)

- Uncontrolled tumour-related pain

- Uncontrolled or symptomatic hypercalcemia

- Malignancies other than TNBC within 5 years prior to randomisation)

- Significant cardiovascular disease, within 3 months prior to randomisation, unstable
arrhythmias, or unstable angina

- Presence of an abnormal ECG

- Severe infection requiring oral or IV antibiotics within 4 weeks prior to
randomisation, including but not limited to hospitalization for complications of
infection, bacteraemia, or severe pneumonia.

- Current treatment with anti-viral therapy for HBV.

- Major surgical procedure within 4 weeks prior to randomisation or anticipation of the
need for a major surgical procedure during the course of the study other than for
diagnosis

- Treatment with investigational therapy within 28 days prior to randomisation

- Pregnant or lactating, or intending to become pregnant during or within 5 months after
the last dose of study treatment

Exclusion Criteria Related to Atezolizumab:

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

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

- History of autoimmune disease

- Prior allogeneic 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
computerised tomography (CT) scan History of radiation pneumonitis in the radiation
field (fibrosis) is permitted.

- Active tuberculosis

- Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or
anticipation that a live, attenuated vaccine will be required during
atezolizumab/placebo treatment or within 5 months after the last dose of
atezolizumab/placebo

- Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or
pathway targeting agents

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

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

Exclusion Criteria Related to Capecitabine:

- Inability to swallow pills

- Malabsorption syndrome, disease significantly affecting gastrointestinal function,
resection of the stomach or small bowel, or ulcerative colitis

- Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and
unexpected reactions to fluoropyrimidine therapy in patients selected to receive
capecitabine

Exclusion Criteria Related to Carboplatin/Gemcitabine:

-Hypersensitivity to platinum containing compounds or any component of carboplatin or
gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine