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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
333
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.
Stanford University Medical Center
Palo Alto, California, United States
Norwalk Hospital
Norwalk, Connecticut, United States
Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital
Carrollton, Georgia, United States
Mercy Medical Center
Baltimore, Maryland, United States
HCA Midwest Division
Kansas City, Missouri, United States
Number of Participants With Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population
Number of participants with Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population. pCR is defined as eradication of invasive tumor from both breast and lymph nodes (ypT0/is ypN0). pCR was evaluated for each participant after neoadjuvant study treatment and surgery. Participants whose pCR assessment was missing will be counted as not achieving a pCR.
Time frame: After neoadjuvant study treatment and surgery, up to primary analysis data cut off on 03 ApriI 2020
Number of Participants With pCR in Subpopulation With PD-L1-Positive Tumor Status (Tumor-infiltrating Immune Cell [IC] 1/2/3) Using AJCC Staging System
Number of participants with Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in the subpopulation with programmed death-ligand1 (PD-L1)-positive tumor status(tumor-infiltrating immune cell \[IC\] IC1/2/3) . pCR is defined as eradication of invasive tumor from both breast and lymph nodes (ypT0/is ypN0). pCR was evaluated for each participant after neoadjuvant study treatment and surgery. Participants whose pCR assessment was missing will be counted as not achieving a pCR.
Time frame: After neoadjuvant study treatment and surgery, up to primary analysis data cut off on 03 ApriI 2020
Event-Free Survival (EFS) in All Participants
Event-free survival (EFS) defined as the time from randomization to the first documented occurrence of disease recurrence, disease progression, or death from any cause in all participants. Recurrent disease includes local, regional, or distant recurrence and contralateral breast cancer. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or recurrent disease.
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Event-Free Survival (EFS) in Subpopulation With PD-L1-Postive Tumor Status
Event-free survival (EFS) defined as the time from randomization to the first documented occurrence of disease recurrence, disease progression, or death from any cause in the subpopulation with PD-L1-positive tumor status. Recurrent disease includes local, regional, or distant recurrence and contralateral breast cancer. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or recurrent disease.
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Disease-Free Survival (DFS) in All Participants Who Undergo Surgery
Disease-free survival (DFS) defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first. DFS is analyzed with the use of the same methodology as specified for EFS for all participants.
Time frame: From surgery and up to study final analysis data cut off on 28 September 2022.
Disease-Free Survival (DFS) in Subpopulation of Participants With PD-L1-Positive Tumor Status Who Undergo Surgery
Disease-free survival (DFS) defined as the time from surgery to the first documented disease recurrence or death from any cause, whichever occurs first. DFS is analyzed with the use of the same methodology as specified for EFS for the subpopulation of participants with PD-L1-positive tumor status.
Time frame: From surgery and up to study final analysis data cut off on 28 September 2022.
Overall Survival (OS) in All Participants
Overall survival (OS) defined as the time from randomization to the date of death from any cause in all participants.
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Overall Survival (OS) in Subpopulation With PD-L1-Positive Tumor Status
Overall survival (OS) defined as the time from randomization to the date of death from any cause in the subpopulation with PD-L1-positive tumor status.
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Mean Scores for Function (Role/Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30
Mean score in function (role, physical) and global health status(GHS)/ health-related quality of life (HRQoL) by cycle and between treatment arms as assessed by the functional and HRQoL scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core30(QLQ C30). The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms).
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Mean Change From Baseline Scores for Function (Role, Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30
Mean change from baseline score in function (role, physical) and global health status(GHS)/ health-related quality of life (HRQoL) by cycle and between treatment arms as assessed by the functional and HRQoL scales of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core30(QLQ C30).
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Percentage of Participants With at Least One Adverse Events (AEs)
Percentage of participants with at least one adverse event.
Time frame: From randomization and up to study final analysis data cut off on 28 September 2022.
Minimum Observed Serum Atezolizumab Concentration (Cmin)
Minimum observed serum atezolizumab concentration.
Time frame: Pre-dose on Day 1 of Cycles 2, 3, 4, 6, 8, 12, and 16 (cycle length = 28 days from Cycles 1 to 5, and 21 days from Cycles 6 to 16)
Maximum Observed Serum Atezolizumab Concentration (Cmax)
Maximum observed atezolizumab concentration (Cmax).
Time frame: Day 1 of Cycle 1 post dose (cycle length = 28 days)
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Percentage of participants with anti-drug antibodies (ADAs) to atezolizumab.
Time frame: Baseline up to approximately 20 months
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The Valley Hospital; Valley Medical Group
Paramus, New Jersey, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street
Chattanooga, Tennessee, United States
Tennessee Oncology
Nashville, Tennessee, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, United States
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