A Study to Investigate Atezolizumab and Chemotherapy Compared With Placebo and Chemotherapy in the Neoadjuvant Setting in Participants With Early Stage Triple Negative Breast Cancer
Condition: Triple-negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody; Placebo; Nab-paclitaxel; Doxorubicin; Cyclophosphamide; Filgrastim; Pegfilgrastim
Intervention description: Atezolizumab was administered as per schedule described in respective arm.; Placebo matched to atezolizumab was administered as per schedule described in respective arm.; Nab-paclitaxel was administered as per schedule described in the arms.; Doxorubicin was administered as per schedule described in the arms.; Cyclophosphamide was administered as per schedule described in the arms.; Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.; Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Atezolizumab; Antibodies
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 333.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a global Phase III, double-blind, randomized, placebo-controlled study designed to
      evaluate the efficacy and safety of neoadjuvant treatment with atezolizumab (anti-programmed
      death-ligand 1 [anti-PD-L1] antibody) and nab-paclitaxel followed by doxorubicin and
      cyclophosphamide (nab-pac-AC), or placebo and nab-pac-AC in participants eligible for surgery
      with initial clinically assessed triple-negative breast cancer (TNBC).
    

Eligibility criteria:

        Inclusion criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Histologically documented TNBC (negative human epidermal growth factor receptor 2
             [HER2], estrogen receptor [ER], and progesterone receptor [PgR] status)

          -  Confirmed tumor programmed death-ligand 1 (PD-L1) evaluation as documented through
             central testing of a representative tumor tissue specimen

          -  Primary breast tumor size of greater than (>) 2 centimeters (cm) by at least one
             radiographic or clinical measurement

          -  Stage at presentation: cT2-cT4, cN0-cN3, cM0

          -  Participant agreement to undergo appropriate surgical management including axillary
             lymph node surgery and partial or total mastectomy after completion of neoadjuvant
             treatment

          -  Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>=) 53
             percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)
             scans

          -  Adequate hematologic and end-organ function

          -  Representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in paraffin
             blocks (preferred) or at least 20 unstained slides, with an associated pathology
             report documenting ER, PgR, and HER2 negativity

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods, and agreement to refrain from
             donating eggs

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures and agreement to refrain from donating sperm

          -  Women who are not postmenopausal or have undergone a sterilization procedure must have
             a negative serum pregnancy test result within 14 days prior to initiation of study
             drug

        Exclusion criteria:

          -  Prior history of invasive breast cancer

          -  Stage 4 (metastatic) breast cancer

          -  Prior systemic therapy for treatment and prevention of breast cancer

          -  Previous therapy with anthracyclines or taxanes for any malignancy

          -  History of ductal carcinoma in situ (DCIS), except for participants treated
             exclusively with mastectomy >5 years prior to diagnosis of current breast cancer

          -  History of pleomorphic lobular carcinoma in situ (LCIS), except for participants
             surgically managed >5 years prior to diagnosis of current breast cancer

          -  Bilateral breast cancer

          -  Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph
             nodes

          -  Axillary lymph node dissection prior to initiation of neoadjuvant therapy

          -  History of other malignancy within 5 years prior to screening, with the exception of
             those with a negligible risk of metastasis or death

          -  Cardiopulmonary dysfunction

          -  History of severe allergic, anaphylactic, or other hypersensitivity reactions to
             chimeric or humanized antibodies or fusion proteins

          -  Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells

          -  Known allergy or hypersensitivity to the components of the formulations of
             atezolizumab, nab-paclitaxel, cyclophosphamide, or doxorubicin, filgrastim or
             pegfilgrastim

          -  Active or history of autoimmune disease or immune deficiency diseases except history
             of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus, and
             dermatologic manifestations of eczema, psoriasis, lichen simplex chronicus, or
             vitiligo (e.g., participants with psoriatic arthritis are excluded)

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
             chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation
             field (fibrosis) is permitted

          -  Positive human immunodeficiency virus (HIV) test at screening

          -  Active hepatitis B and hepatitis C virus infection

          -  Active tuberculosis

          -  Severe infections within 4 weeks prior to initiation of study treatment, including but
             not limited to hospitalization for complications of infection, bacteremia, or severe
             pneumonia

          -  Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation
             of study treatment, except prophylactic antibiotics

          -  Major surgical procedure within 4 weeks prior to initiation of study treatment or
             anticipation of need for a major surgical procedure during the course of the study

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Administration of a live attenuated vaccine within 4 weeks prior to initiation of
             study treatment or anticipation of need for such a vaccine during the study

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the participant at high risk from treatment
             complications

          -  Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
             checkpoint-blockade therapies, including anti-cluster of differentiation 40
             (anti-CD40), anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4),
             anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies

          -  Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the
             drug, whichever is longer, prior to initiation of study treatment

          -  Treatment with systemic immunosuppressive medications within 2 weeks prior to
             initiation of study treatment or anticipation of need for systemic immunosuppressive
             medications during the study

          -  History of cerebrovascular accident within 12 months prior to randomization

          -  Pregnant or lactating, or intending to become pregnant during the study