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Purpose

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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Atezolizumab and Chemotherapy 		Participants received atezolizumab (840 milligrams [mg]) via intravenous (IV) infusion every 2 weeks in combination with nab-paclitaxel (125 milligrams per square meter [mg/m^2]) via IV infusion every week for 12 weeks, followed by atezolizumab (840 mg) every 2 weeks in combination with doxorubicin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants continued to receive unblinded atezolizumab post-surgery at a fixed dose of 1200 mg by IV infusion every 3 weeks for 11 doses, for a total of approximately 12 months of atezolizumab therapy.
  • Drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody
    Atezolizumab was administered as per schedule described in respective arm.
  • Drug: Nab-paclitaxel
    Nab-paclitaxel was administered as per schedule described in the arms.
  • Drug: Doxorubicin
    Doxorubicin was administered as per schedule described in the arms.
  • Drug: Cyclophosphamide
    Cyclophosphamide was administered as per schedule described in the arms.
  • Drug: Filgrastim
    Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.
  • Drug: Pegfilgrastim
    Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.
Placebo Comparator
Placebo and Chemotherapy 		Participants received placebo matched to atezolizumab via IV infusion every 2 weeks in combination with nab-paclitaxel (125 mg/m^2) via IV infusion every week for 12 weeks, followed by placebo matched to atezolizumab every 2 weeks in combination with doxorubicin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) every 2 weeks via IV infusions with filgrastim/pegfilgrastim support for 4 doses. Participants will be unblinded post-surgery and will continue to be followed.
  • Drug: Placebo
    Placebo matched to atezolizumab was administered as per schedule described in respective arm.
  • Drug: Nab-paclitaxel
    Nab-paclitaxel was administered as per schedule described in the arms.
  • Drug: Doxorubicin
    Doxorubicin was administered as per schedule described in the arms.
  • Drug: Cyclophosphamide
    Cyclophosphamide was administered as per schedule described in the arms.
  • Drug: Filgrastim
    Filgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.
  • Drug: Pegfilgrastim
    Pegfilgrastim was administered according to local prescribing information as determined by the Investigator for 4 doses after completion of initial 12 weeks.

More Details

Status
Completed
Sponsor
Hoffmann-La Roche

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.