A Study of Atezolizumab and Paclitaxel Versus Placebo and Paclitaxel in Participants With Previously Untreated Locally Advanced or Metastatic Triple Negative Breast Cancer (TNBC)
Condition: Triple-Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody; Atezolizumab Placebo; Paclitaxel
Intervention description: Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.; Placebo matching to atezolizumab will be administered via IV infusion on Days 1 and 15 (± 3 days) of every 28-day cycle.; Paclitaxel will be administered at a dose of 90 mg/m^2 via IV infusion on Days 1, 8, and 15 of every 28-day cycle.
Intervention MeSH terms: Paclitaxel; Atezolizumab; Antibodies; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: The Sponsor and its agents; the study site personnel, including the investigator; and the participant will be blinded to treatment assignment.
Enrollment: 653.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This Phase 3, multicenter, randomized, double-blind, placebo controlled study is designed to
      evaluate the efficacy and safety of atezolizumab (MPDL3280A, an anti-programmed death-ligand
      1 [PD-L1] antibody) administered in combination with paclitaxel compared with placebo in
      combination with paclitaxel in participants with previously untreated, inoperable locally
      advanced or metastatic, centrally confirmed TNBC. Participants will be randomized in a 2:1
      ratio to receive atezolizumab or placebo plus paclitaxel until disease progression or
      unacceptable toxicity or end of study, whichever occurs first (maximum up to approximately 40
      months). In addition, the Sponsor may decide to terminate the study at any time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with locally advanced or metastatic, histologically documented TNBC
             (absence of human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER],
             and progesterone receptor [PR] expression), not amenable to surgical therapy

          -  Participants eligible for taxane monotherapy

          -  No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for
             inoperable locally advanced or metastatic TNBC

          -  Availability of formalin-fixed paraffin-embedded (FFPE) tumor block (preferred) or at
             least 17 unstained slides, collected ≤3 months prior to randomization, with an
             associated pathology report, if available. If a tumour sample taken within 3 months
             before randomisation is not available and a tumour biopsy is not clinically feasible,
             the primary surgical resection sample or the most recent FFPE tumour biopsy sample may
             be used. Of these additional options, the most recent sample should be used.

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Life expectancy at least 12 weeks

          -  Measurable disease, as defined by RECIST v1.1

          -  Adequate hematologic and end-organ function

          -  Negative human immunodeficiency virus (HIV) test at screening.

          -  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. The HCV RNA test will be
             performed only for patients who have a positive HCV antibody test.

          -  Women of child bearing potential must have a negative serum pregnancy test result
             within 7 days prior to initiation of study drug

          -  For men and women of child bearing potential: agreement to remain abstinent or use
             protocol defined contraceptive measures during the treatment period and for at least 5
             months after the last dose of atezolizumab/placebo, or for at least 6 months after the
             last dose of paclitaxel

        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 at least 2 weeks prior to randomization

          -  Known central nervous system (CNS) disease, except for treated asymptomatic CNS
             metastases

          -  Leptomeningeal disease

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites

          -  Uncontrolled tumor-related pain, or uncontrolled hypercalcemia or clinically
             significant (symptomatic) hypercalcemia

          -  Malignancies other than TNBC within 5 years prior to randomization, with the exception
             of those with a negligible risk of metastasis or death and treated with expected
             curative outcome (such as adequately treated carcinoma in situ of the cervix,
             non-melanoma skin carcinoma, or Stage I uterine cancer)

          -  Pregnant or breast-feeding women, or intending to become pregnant during the study

          -  Evidence of significant uncontrolled concomitant disease that could affect compliance
             with the protocol or interpretation of results, including significant liver disease,
             cardiovascular disease, and presence of an abnormal electrocardiogram (ECG)

          -  Serious infection requiring antibiotics within 2 weeks prior to randomization,
             including but not limited to infections requiring hospitalization or IV antibiotics,
             such as bacteremia, or severe pneumonia

          -  Major surgical procedure within 4 weeks prior to randomization or anticipation of the
             need for a major surgical procedure during the study other than for diagnosis

          -  Treatment with investigational therapy within 30 days prior to initiation of study
             treatment

          -  History of hypersensitivity reactions to study drug or any component of the study drug
             formulation