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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
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

NCT03197935

CompletedPhase 3

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).

Eligibility overview

Sex: ALL

Age: 18 Years to

Healthy volunteers: No

Study type: INTERVENTIONAL

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
Locations (68)
  • 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