A Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Participants With Triple-Negative Breast Cancer

Study Overview
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Brief Summary
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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).

Official Title
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A Phase Ib, Open-Label, Multicohort Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Patients With Triple-Negative Breast Cancer

Conditions
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Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: Tiragolumab
* Drug: Atezolizumab
* Drug: Nab-paclitaxel
* Drug: Tiragolumab
* Drug: Atezolizumab
* Drug: Nab-paclitaxel
* Drug: Carboplatin
* Drug: Doxorubicin
* Drug: Cyclophosphamide
* Drug: Granulocyte colony-stimulating factor (G-CSF)
* Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel<br>Participants with first-line metastatic TNBC will receive tiragolumab and atezolizumab on Day 1 of every 28-day cycle plus nab-paclitaxel on Days 1, 8, and 15 of every 28-day cycle. | Drug: Tiragolumab<br>* Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.<br>Drug: Atezolizumab<br>* Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.<br>* Other names: Tecentriq;Drug: Nab-paclitaxel<br>* 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.<br>* Other names: Abraxane;|
| Experimental: Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC<br>Participants with early TNBC in the neoadjuvant setting, who are eligible for surgery, will receive tiragolumab and atezolizumab every 2 weeks (Q2W) in combination with nab-paclitaxel weekly (QW) and carboplatin every 3 weeks (Q3W) for four cycles, followed by tiragolumab and atezolizumab in combination with doxorubicin and cyclophosphamide Q2W with granulocyte colony-stimulating factor (G-CSF; filgrastim or pegfilgrastim) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for four doses. | Drug: Tiragolumab<br>* Tiragolumab 420 mg administered by IV infusion Q2W.<br>Drug: Atezolizumab<br>* Atezolizumab 840 mg administered by IV infusion Q2W.<br>* Other names: Tecentriq;Drug: Nab-paclitaxel<br>* Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.<br>* Other names: Abraxane;Drug: Carboplatin<br>* Carboplatin (area under the concentration-time curve [AUC]: 5 milligrams per milliliter per minute [mg/mL/min]) administered by IV infusion Q3W.<br>Drug: Doxorubicin<br>* Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.<br>* Other names: Lipodox, Doxil;Drug: Cyclophosphamide<br>* Cyclophosphamide 600 mg/m^2 Q2W administered by IV infusion.<br>Drug: Granulocyte colony-stimulating factor (G-CSF)<br>* G-CSF support for four doses.<br>* Other names: filgrastim, pegfilgrastim;Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)<br>* GM-CSF support for four doses.<br>|
| Experimental: Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC<br>Participantswith early TNBC in the neoadjuvant setting, who are eligible for surgery, will receive tiragolumab and atezolizumab Q2W in combination with nab-paclitaxel QW for 12 weeks, followed by tiragolumab and atezolizumab in combination with doxorubicin and cyclophosphamide Q2W with G-CSF (filgrastim or pegfilgrastim) or GM-CSF support for four doses. | Drug: Tiragolumab<br>* Tiragolumab 420 mg administered by IV infusion Q2W.<br>Drug: Atezolizumab<br>* Atezolizumab 840 mg administered by IV infusion Q2W.<br>* Other names: Tecentriq;Drug: Nab-paclitaxel<br>* Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.<br>* Other names: Abraxane;Drug: Doxorubicin<br>* Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.<br>* Other names: Lipodox, Doxil;Drug: Cyclophosphamide<br>* Cyclophosphamide 600 mg/m^2 Q2W administered by IV infusion.<br>Drug: Granulocyte colony-stimulating factor (G-CSF)<br>* G-CSF support for four doses.<br>* Other names: filgrastim, pegfilgrastim;Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)<br>* GM-CSF support for four doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (Cohort A) |  | Up to approximately 21 months | 
| Progression-free Survival (Cohort A) |  | Up to approximately 21 months | 
| Duration of Response (Cohort A) |  | Up to approximately 21 months | 
| Overall Survival (Cohort A) |  | Up to approximately 21 months | 
| Serum Concentrations of Tiragolumab | TD visit: treatment discontinuation visit | 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 | 
| 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 | 
| 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 | 
| 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 |