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Sponsor: Hoffmann-La Roche
Conditions: Triple-negative Breast Cancer
Interventions: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody, Placebo, Nab-paclitaxel, Doxorubicin, Cyclophosphamide
Countries: United States, Australia, Belgium, Brazil, Canada, Germany, Italy, Japan
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).
Sex: ALL
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
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
- Palo Alto, California, United States
- Norwalk, Connecticut, United States
- Carrollton, Georgia, United States
- Baltimore, Maryland, United States
- Kansas City, Missouri, United States
- Paramus, New Jersey, United States
- New York, New York, United States
- Chattanooga, Tennessee, United States
- Nashville, Tennessee, United States
- Nashville, Tennessee, United States
- Fort Worth, Texas, United States
- Spokane, Washington, United States
- Clayton, Victoria, Australia
- Bull Creek, Western Australia, Australia
- Brussels, Belgium
- Leuven, Belgium
- Namur, Belgium
- Wilrijk, Belgium
- Salvador, Estado de Bahia, Brazil
- Goiânia, Goiás, Brazil
- Uberaba, Minas Gerais, Brazil
- Curitiba, Paraná, Brazil
- Rio de Janeiro, Rio de Janeiro, Brazil
- Porto Alegre, Rio Grande do Sul, Brazil
- Porto Alegre, Rio Grande do Sul, Brazil
- São Paulo, São Paulo, Brazil
- Montreal, Quebec, Canada
- Montreal, Quebec, Canada
- Québec, Quebec, Canada
- Bad Nauheim, Germany
- + 38 more on CT.gov