This is a Phase Ib, open-label, two-stage study with two active regimens in each stage designed to evaluate the safety and tolerability of combination treatment with atezolizumab, trastuzumab, and pertuzumab (with and without docetaxel) or atezolizumab and trastuzumab emtansine in participants with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) and locally advanced early breast cancer (EBC), and atezolizumab with doxorubicin and cyclophosphamide in HER2-negative breast cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
98
Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.
Carboplatin will be administered at an initial target of area under the curve (AUC) of 6 milligrams per milliliter\*min (mg/mL\*min) via an IV infusion on Day 1 of every 21-days for 6 cycles.
Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.
Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).
Doxorubicin will be administered at 60 mg/m\^2 every 2 weeks as an IV bolus over 3 to 5 minutes or as an infusion over 15 to 30 minutes.
Cyclophosphamide will be administered at 600 mg/m\^2 on Day 1 of each 21 day cycle as an IV bolus over 3 to 5 minutes or as an infusion, in accordance with local policy.
University of Alabama at Birmingham
Birmingham, Alabama, United States
University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute
Little Rock, Arkansas, United States
Joliet oncology hematology associates
Joliet, Illinois, United States
Horizon Oncology Research, Inc.
Lafayette, Indiana, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Karmanos Cancer Center; Department of Oncology
Detroit, Michigan, United States
HCA Midwest Division
Kansas City, Missouri, United States
Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart
The Bronx, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Duke Cancer Center
Durham, North Carolina, United States
...and 10 more locations
Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F
Time frame: Baseline up to Day 21
Percentage of Participants With DLT - Cohort 1E
Time frame: Baseline up to Day 28
Percentage of Participants With Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for AEs, Version 4.0 (NCI CTCAE V4.0)
Time frame: Baseline up to approximately 3 years
Maximum Serum Concentration (Cmax) of Atezolizumab
Cohorts 1A, 1B, 1C, 1D, E1, 1F, 2A, 2B, 2C, 2D: 30 minutes after end of infusion on Day 1 Cycle 1 (cycle length=21 days); pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3 (except cohort 1E), 4, 8, on Day 1 of every 8 cycles until study treatment/early discontinuation, 120 days after treatment completion/discontinuation (up to approximately 3 years)
Time frame: Cohorts 1A, 1B, 1C, 1D, E1, 1F, 2A, 2B, 2C, 2D: pre-infusion (Hour 0), 30 minutes after end of atezolimumab infusion on Day 1 Cycle 1 (cycle length=21 days) up to approximately 3 years (detailed timeframe provided in measure description)
Minimum Serum Concentration (Cmin) of Atezolizumab
Time frame: pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3 (except cohort 1E), 4, 8 (cycle length=21 days), on Day 1 of every 8 cycles until study treatment/early discontinuation, 120 days after treatment completion/discontinuation (up to approximately 3 years)
Cmin of Trastuzumab
Time frame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
Cmin of Trastuzumab Emtansine
Time frame: Cohorts 1B, 1C, 1D, 2B, 2C: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
Cmin of Pertuzumab
Time frame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
Cmin of Doxorubicin
Time frame: Cohort 1E: at the end of doxorubicin infusion, 4 and 8 hours after doxorubicin infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days)
Cmin of Cyclophosphamide
Time frame: Cohort 1E: at the end of cyclophosphamide infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days), 4 and 8 hours after cyclophosphamide infusion on Day 1 of Cycle 1
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Atezolimumab
Time frame: pre-infusion (Hour 0) on Day 1 of Cycle 1, 2, 3 (except cohort 1E), 4, 8 (cycle length=21 days), on Day 1 of every 8 cycles until study treatment/early discontinuation, 120 days after treatment completion/discontinuation (up to approximately 3 years)
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab
Time frame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
Time frame: Cohorts 1B, 1C, 1D, 2B, 2C: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Pertuzumab
Time frame: Cohorts 1A, 1F, 2A, 2D: pre-infusion (Hour 0) on Day 1 of Cycle 1, 3 (cycle length=21 days), at study treatment/early discontinuation, 120 days after treatment completion or discontinuation (up to approximately 3 years)
Number of Treatment Cycles Received
Time frame: Baseline up to approximately 3 years
Percentage of Participants With Various Dose Intensity
Time frame: Baseline up to approximately 3 year
Plasma Concentration of Doxorubicin
Time frame: Cohort 1E: at the end of doxorubicin infusion, 4 and 8 hours after doxorubicin infusion on Day 1 Cycle 1 and 4 (cycle length=21 days)
Plasma Concentration of Cyclophosphamide
Time frame: Cohort 1E: at the end of cyclophosphamide infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days), 4 and 8 hours after cyclophosphamide infusion on Day of Cycle 1
Plasma Concentration of 4-Hydroxycyclophosphamide
Time frame: Cohort 1E: at the end of cyclophosphamide infusion on Day 1 of Cycle 1 and 4 (cycle length=21 days), 4 and 8 hours after cyclophosphamide infusion on Day of Cycle 1
Plasma Concentration of Docetaxel
Time frame: Cohort 1F: at the end of docetaxel infusion, 4 and 8 hours after docetaxel infusion on Day 1 Cycle 1 and 3 (cycle length=21 days)
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