Triple-Negative Breast Cancer
Conditions
Brief summary
The purpose of this study is to evaluate the safety, efficacy, and pharmacokinetics of tiragolumab in combination with atezolizumab and chemotherapy in participants with metastatic and early triple-negative breast cancer (TNBC).
Interventions
DRUGTiragolumab
Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.
DRUGAtezolizumab
Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.
DRUGNab-paclitaxel
Nab-paclitaxel 100 milligrams per square meter (mg/m\^2) administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
DRUGCarboplatin
Carboplatin (area under the concentration-time curve \[AUC\]: 5 milligrams per milliliter per minute \[mg/mL/min\]) administered by IV infusion Q3W.
DRUGDoxorubicin
Doxorubicin 60 mg/m\^2 Q2W administered by IV infusion.
DRUGCyclophosphamide
Cyclophosphamide 600 mg/m\^2 Q2W administered by IV infusion.
G-CSF support for four doses.
GM-CSF support for four doses.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Cohort A: * Metastatic or locally advanced unresectable, histologically documented TNBC characterized by absence of human epidermal growth factor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) expression * Only patients with metastatic TNBC tumors that are centrally tested and found to be programmed death-ligand 1 (PD-L1) positive will be enrolled * No prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic TNBC * Eastern Cooperative Oncology Group performance status of 0 or 1 * Measurable disease, as assessed by the investigator according to RECIST v1.1 * Adequate hematologic and end-organ function Cohort B: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically documented TNBC (negative HER2, ER, and PR status) * Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen * Primary breast tumor size of greater than (\>) 2 centimeters (cm) by at least one radiographic or clinical measurement * Stage at presentation: cT2-cT4, cN0-cN3, cM0 * Baseline left ventricular ejection fraction (LVEF) greater than or equal to (\>/=) 53 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans * Adequate hematologic and end-organ function
Exclusion criteria
Cohort A: * Formalin-fixed, paraffin-embedded (FFPE) tumor tissue that is PD-L1 negative, as determined on the SP142 PD-L1 immunohistochemistry assay, with positivity defined as immune cells greater than or equal to (\>/=) 1% * Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>2 weeks prior to initiation of study treatment * Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases * Leptomeningeal disease Cohort B: * History of invasive breast cancer * Stage IV (metastatic) breast cancer * Prior systemic therapy for treatment and prevention of breast cancer * Previous therapy with anthracyclines, platinum, or taxanes for any malignancy * Synchronous, bilateral invasive breast cancer * Cardiopulmonary dysfunction
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (Cohort B) | Up to approximately 21 months |
| Confirmed Objective Response Rate ORR (Cohort A) | Up to approximately 21 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (Cohort A) | Up to approximately 21 months | — |
| Overall Survival (Cohort A) | Up to approximately 21 months | — |
| Serum Concentrations of Tiragolumab | Cohort A: Day 1 of Cycles (cycle=28 days) 1, 2, 3, 4, 8, 12, and 16 and at TD visit from start of treatment up to approximately 17 months; Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | TD visit: treatment discontinuation visit |
| Serum Concentrations of Atezolizumab | Cohort A: Day 1 of Cycles (cycle=28 days) 1, 2, 3, 4, 8, 12, and 16 and at TD visit from start of treatment up to approximately 17 months; Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Plasma Concentrations of Nab-paclitaxel (Cohort B) | Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Percentage of Participants With Adverse Events (Cohort A) | Up to approximately 21 months | — |
| Plasma Concentrations of Doxorubicin (Cohort B) | Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Plasma Concentrations of Cyclophosphamide (Cohort B) | Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab | Cohort A: Day 1 of Cycles (cycle=28 days) 1, 2, 3, 4, 8, 12, and 16 and at TD visit from start of treatment up to approximately 17 months; Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Percentage of Participants With ADAs to Atezolizumab | Cohort A: Day 1 of Cycles (cycle=28 days) 1, 2, 3, 4, 8, 12, and 16 and at TD visit from start of treatment up to approximately 17 months; Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Plasma Concentrations of Carboplatin (Cohort B) | Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months | — |
| Progression-free Survival (Cohort A) | Up to approximately 21 months | — |
Countries
Australia, Brazil, Germany, Russia, South Korea, Spain, Taiwan, United States
Outcome results
None listed