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Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic |
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Documented disease progression occurring within 12 months from the last treatment with curative intent |
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Prior treatment (of early breast cancer) with an anthracycline and taxane |
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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 |
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Measurable or non-measurable disease, as defined by RECIST 1.1 |
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Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used |
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Eastern Cooperative Oncology Group performance status 0-1 |
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Life expectancy ≥ 12 weeks |
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Adequate haematologic and end-organ function |
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Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening |
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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 |
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The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test |
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Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening |
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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 atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period |
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Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm |
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Inclusion criteria for patients enrolled after the recruitment of all-comers |
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is complete |
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PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 |
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expression on tumour-infiltrating immune cells (IC) of 1% or greater |
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Spinal cord compression not definitively treated with surgery and/or radiation, or
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Symptomatic or rapid visceral progression
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previously diagnosed and treated spinal cord compression without evidence that disease
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No prior treatment with an anthracycline and taxane
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has been clinically stable for > 2 weeks prior to randomisation
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History of leptomeningeal disease
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Symptomatic, untreated, or actively progressing central nervous system (CNS)
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metastases
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Uncontrolled tumour-related pain
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Uncontrolled or symptomatic hypercalcemia
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Malignancies other than TNBC within 5 years prior to randomisation)
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Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
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Presence of an abnormal ECG
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drainage procedures (once monthly or more frequently) (patients with indwelling
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catheters such as PleurX® are allowed)
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Current treatment with anti-viral therapy for HBV
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Treatment with investigational therapy within 28 days prior to randomisation
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Significant cardiovascular disease, within 3 months prior to randomisation, unstable
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Exclusion Criteria Related to Atezolizumab
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arrhythmias, or unstable angina
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Severe infection requiring oral or IV antibiotics within 4 weeks prior to
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History of autoimmune disease
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randomisation, including but not limited to hospitalization for complications of
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Prior allogeneic stem cell or solid organ transplantation
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infection, bacteraemia, or severe pneumonia
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Active tuberculosis
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Major surgical procedure within 4 weeks prior to randomisation or anticipation of the
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need for a major surgical procedure during the course of the study other than for
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diagnosis
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Pregnant or lactating, or intending to become pregnant during or within 5 months after
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Exclusion Criteria Related to Capecitabine
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the last dose of atezolizumab, or within 6 months after the last dose of capecitabine
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Inability to swallow pills
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whichever is later
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History of severe allergic, anaphylactic, or other hypersensitivity reactions to
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Exclusion Criteria Related to Carboplatin/Gemcitabine
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chimeric or humanised antibodies or fusion proteins
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Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
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ovary cells or to any component of the atezolizumab formulation
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History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced
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pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic
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organizing pneumonia), or evidence of active pneumonitis on screening chest
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computerised tomography (CT) scan History of radiation pneumonitis in the radiation
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field (fibrosis) is permitted
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Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or
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anticipation that a live, attenuated vaccine will be required during
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atezolizumab/placebo treatment or within 5 months after the last dose of
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atezolizumab/placebo
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Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or
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pathway targeting agents
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Treatment with systemic immunostimulatory agents (including but not limited to
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interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug
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(whichever is longer) prior to randomisation
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Treatment with systemic corticosteroids or other systemic immunosuppressive
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medications within 2 weeks prior to start of study treatment, or anticipated
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requirement for systemic immunosuppressive medications during the trial
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Malabsorption syndrome, disease significantly affecting gastrointestinal function
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resection of the stomach or small bowel, or ulcerative colitis
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Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and
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unexpected reactions to fluoropyrimidine therapy in patients selected to receive
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capecitabine
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Hypersensitivity to platinum containing compounds or any component of carboplatin or
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gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine
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