Clinical Trials List
Protocol NumberCO42177
NCT Number(ClinicalTrials.gov Identfier)NCT04584112
2020-08-01 - 2023-06-30
Phase I
Recruiting2
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
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Trial Applicant
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Sponsor
Hoffmann-La Roche
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chih-Jung Chen Division of General Surgery
- Chen-Teng Wu Division of General Surgery
- Liang-Chih Liu Division of General Surgery
- Yao-Chung Wu Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 郭文宏 Division of General Surgery
- 蔡立威 Division of General Surgery
- 林柏翰 Division of General Internal Medicine
- 羅喬 Division of General Surgery
- 張端瑩 Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
- SUNG-HSIN KUO Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- MING-YANG WANG Division of General Surgery
- YEN-SHEN LU Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Triple-Negative Breast Cancer
Objectives
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).
Test Drug
Tiragolumab；Atezolizumab
Active Ingredient
Atezolizumab
Tiragolumab
Tiragolumab
Dosage Form
IVT
IVT
IVT
Dosage
600mg/10ml
840mg/14ml
840mg/14ml
Endpoints
Primary Outcome Measures :
Percentage of Participants With Adverse Events (Cohort B) [ Time Frame: Up to approximately 21 months ]
Confirmed Objective Response Rate ORR (Cohort A) [ Time Frame: Up to approximately 21 months ]
Secondary Outcome Measures :
Percentage of Participants With Adverse Events (Cohort A) [ Time Frame: Up to approximately 21 months ]
Progression-free Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
Duration of Response (Cohort A) [ Time Frame: Up to approximately 21 months ]
Overall Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
Serum Concentrations of Tiragolumab [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Adverse Events (Cohort B) [ Time Frame: Up to approximately 21 months ]
Confirmed Objective Response Rate ORR (Cohort A) [ Time Frame: Up to approximately 21 months ]
Secondary Outcome Measures :
Percentage of Participants With Adverse Events (Cohort A) [ Time Frame: Up to approximately 21 months ]
Progression-free Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
Duration of Response (Cohort A) [ Time Frame: Up to approximately 21 months ]
Overall Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
Serum Concentrations of Tiragolumab [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 ]
Inclution Criteria
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
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
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
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
The Estimated Number of Participants
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Taiwan
8 participants
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Global
60 participants
