Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
Phase 1
Completed
- Conditions
- HER2-Positive Metastatic Breast CancerHER2-Negative Metastatic Breast CancerLocally Advanced or Early Breast Cancer
- Interventions
- Registration Number
- NCT02605915
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 98
Inclusion Criteria
- Histologically documented HER2-positive and HER2-negative (cohort E only) breast cancer
- Metastatic breast cancer that is measurable (Stage 1) or early breast cancer with a primary tumor size greater than (>) 2 centimeter (cm) (Stage 2)
- Eastern cooperative oncology group (ECOG) performed status of 0, 1 or 2; 0 or 1 (cohort E only)
- Life expectancy of 12 or more weeks
- Adequate hematologic and end-organ function
- Left ventricular ejection fraction greater than or equal to (>=) 50 percentage (%); >=55% (cohort E only)
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Exclusion Criteria
- Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
- Leptomeningeal disease
- Pregnancy or lactation
- History of autoimmune disease
- Prior allogeneic stem cell or solid organ transplantation
- Positive test for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab Atezolizumab Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks. Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab Pertuzumab Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks. Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab Trastuzumab Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks. Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg Atezolizumab Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks. Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg Trastuzumab emtansine Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks. Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg Atezolizumab Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks. Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg Atezolizumab Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks. Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg Trastuzumab emtansine Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks. Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide Doxorubicin Participants with HER2-negative breast cancer will receive atezolizumab (every 2 weeks) in combination with doxorubicin (every 2 weeks) and cyclophosphamide for four cycles. After the completion of four cycles of combination atezolizumab /doxorubicin / cyclophosphamide, atezolizumab will be continued as a single-agent at a dose of 1200 mg every 3 weeks. Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide Cyclophosphamide Participants with HER2-negative breast cancer will receive atezolizumab (every 2 weeks) in combination with doxorubicin (every 2 weeks) and cyclophosphamide for four cycles. After the completion of four cycles of combination atezolizumab /doxorubicin / cyclophosphamide, atezolizumab will be continued as a single-agent at a dose of 1200 mg every 3 weeks. Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab Pertuzumab Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2C: Safety Expansion Trastuzumab emtansine Participants with HER2-positive metastatic breast cancer/unresectable locally advanced breast cancer who received prior treatment with trastuzumab and a taxane chemotherapy will receive atezolizumab in combination with trastuzumab emtansine at the dose determined from stage 1, every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity. Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg Trastuzumab emtansine Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks. Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel Atezolizumab Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide Atezolizumab Participants with HER2-negative breast cancer will receive atezolizumab (every 2 weeks) in combination with doxorubicin (every 2 weeks) and cyclophosphamide for four cycles. After the completion of four cycles of combination atezolizumab /doxorubicin / cyclophosphamide, atezolizumab will be continued as a single-agent at a dose of 1200 mg every 3 weeks. Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel Pertuzumab Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel Docetaxel Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab Atezolizumab Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel Trastuzumab Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab Carboplatin Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab Docetaxel Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab Trastuzumab Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2B: Atezolizumab/Trastuzumab emtansine Carboplatin Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2B: Atezolizumab/Trastuzumab emtansine Atezolizumab Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2B: Atezolizumab/Trastuzumab emtansine Pertuzumab Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2B: Atezolizumab/Trastuzumab emtansine Trastuzumab emtansine Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2B: Atezolizumab/Trastuzumab emtansine Docetaxel Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2B: Atezolizumab/Trastuzumab emtansine Trastuzumab Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. Cohort 2C: Safety Expansion Atezolizumab Participants with HER2-positive metastatic breast cancer/unresectable locally advanced breast cancer who received prior treatment with trastuzumab and a taxane chemotherapy will receive atezolizumab in combination with trastuzumab emtansine at the dose determined from stage 1, every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity. Cohort 2D: Safety Expansion Atezolizumab Participants with HER2-positive metastatic breast cancer recently progressed on an HP containing regimen will receive atezolimumab in combination with trastuzumab and pertuzumab every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity. Cohort 2D: Safety Expansion Trastuzumab Participants with HER2-positive metastatic breast cancer recently progressed on an HP containing regimen will receive atezolimumab in combination with trastuzumab and pertuzumab every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity. Cohort 2D: Safety Expansion Pertuzumab Participants with HER2-positive metastatic breast cancer recently progressed on an HP containing regimen will receive atezolimumab in combination with trastuzumab and pertuzumab every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F Baseline up to Day 21 Percentage of Participants With Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for AEs, Version 4.0 (NCI CTCAE V4.0) Baseline up to approximately 3 years Percentage of Participants With DLT - Cohort 1E Baseline up to Day 28
- Secondary Outcome Measures
Name Time Method Minimum Serum Concentration (Cmin) of Atezolizumab 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 Pertuzumab 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 Baseline up to approximately 3 years Percentage of Participants With Various Dose Intensity Baseline up to approximately 3 year Maximum Serum Concentration (Cmax) of Atezolizumab 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) 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)
Cmin of Trastuzumab 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 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 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 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 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 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) Plasma Concentration of Doxorubicin 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 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 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 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) Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab 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 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)
Trial Locations
- Locations (20)
HCA Midwest Division
🇺🇸Kansas City, Missouri, United States
Horizon Oncology Research, Inc.
🇺🇸Lafayette, Indiana, United States
St. Luke's University Health Network
🇺🇸Bethlehem, Pennsylvania, United States
West Clinic
🇺🇸Germantown, Tennessee, United States
Kimmel Cancer Center Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Cancer Therapy and Research Center CTRC at UTHSCSA
🇺🇸San Antonio, Texas, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Karmanos Cancer Center; Department of Oncology
🇺🇸Detroit, Michigan, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
Oncology Hematology Care Inc
🇺🇸Cincinnati, Ohio, 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
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart
🇺🇸Bronx, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street
🇺🇸Chattanooga, Tennessee, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
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