HER2-Negative Metastatic Breast Cancer, HER2-Positive Metastatic Breast Cancer, Locally Advanced or Early Breast Cancer
Conditions
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.
Interventions
DRUGAtezolizumab
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.
DRUGCarboplatin
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.
DRUGDocetaxel
Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
DRUGPertuzumab
Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
DRUGTrastuzumab
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.
DRUGTrastuzumab emtansine
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).
DRUGDoxorubicin
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.
DRUGCyclophosphamide
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F | Baseline up to Day 21 |
| Percentage of Participants With DLT - Cohort 1E | 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) | Baseline up to approximately 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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) | — |
| 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) | — |
| 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 | — |
| Number of Treatment Cycles Received | Baseline up to approximately 3 years | — |
| Percentage of Participants With Various Dose Intensity | Baseline up to approximately 3 year | — |
| 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 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) | — |
| 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) |
| 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) | — |
Countries
United States
Outcome results
None listed