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

Not Recruiting

Trial ID: NCT03197935


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).

Official Title

A Phase III Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Neoadjuvant Anthracycline/Nab-Paclitaxel-Based Chemotherapy Compared With Placebo and Chemotherapy in Patients With Primary Invasive Triple-Negative Breast Cancer

Stanford Investigator(s)

Melinda L. Telli, M.D.
Melinda L. Telli, M.D.

Professor of Medicine (Oncology)


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

   - Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>=) 53
   percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA)

   - 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

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

   - 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

   - 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

   - 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

   - 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


drug: Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody

drug: Placebo

drug: Nab-paclitaxel

drug: Doxorubicin

drug: Cyclophosphamide

drug: Filgrastim

drug: Pegfilgrastim

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kaitlin Zablotsky

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