Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer
Purpose
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.
Conditions
- HER2-Positive Metastatic Breast Cancer
- HER2-Negative Metastatic Breast Cancer
- Locally Advanced or Early Breast Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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)
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
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab |
Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks. |
|
Experimental Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg |
Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks. |
|
Experimental Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg |
Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks. |
|
Experimental Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg |
Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks. |
|
Experimental Cohort 1E: Atezolizumab/ doxorubicin/ 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. |
|
Experimental Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel |
Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. |
|
Experimental Cohort 2A: Atezolizumab/Trastuzumab/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. |
|
Experimental Cohort 2B: Atezolizumab/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. |
|
Experimental Cohort 2C: Safety Expansion |
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. |
|
Experimental Cohort 2D: Safety Expansion |
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. |
|
More Details
- Status
- Completed
- Sponsor
- Hoffmann-La Roche