A Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Participants With Triple-Negative Breast Cancer
Phase 1
Completed
- Conditions
- Triple-Negative Breast Cancer
- Interventions
- Drug: Granulocyte colony-stimulating factor (G-CSF)Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
- Registration Number
- NCT04584112
- Lead Sponsor
- Hoffmann-La Roche
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
Inclusion Criteria
Not provided
Exclusion Criteria
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Tiragolumab 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Nab-paclitaxel 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Granulocyte colony-stimulating factor (G-CSF) 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. Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel Nab-paclitaxel 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Atezolizumab 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Nab-paclitaxel 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Tiragolumab 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Granulocyte colony-stimulating factor (G-CSF) 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Granulocyte-macrophage colony-stimulating factor (GM-CSF) 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Granulocyte-macrophage colony-stimulating factor (GM-CSF) 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. Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel Tiragolumab 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. Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel Atezolizumab 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Carboplatin 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Doxorubicin 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC Cyclophosphamide 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Atezolizumab 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Doxorubicin 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. Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC Cyclophosphamide 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.
- Primary Outcome Measures
Name Time Method 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
Name Time Method Progression-free Survival (Cohort A) Up to approximately 21 months Overall Survival (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 Percentage of Participants With Adverse Events (Cohort A) Up to approximately 21 months Duration of Response (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
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 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 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
Trial Locations
- Locations (24)
Tennessee Onc., PLLC - SCRI
🇺🇸Nashville, Tennessee, United States
Mater Hospital; Cancer Services
🇦🇺South Brisbane, Queensland, Australia
Hospital SÃrio-Libanês
🇧🇷Sao Paulo, SP, Brazil
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
🇧🇷Sao Paulo, SP, Brazil
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
🇧🇷Goiania, GO, Brazil
Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
🇩🇪Essen, Germany
Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
🇩🇪Heidelberg, Germany
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Arhangelsk, Russian Federation
SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Blokhin Cancer Research Center; Combined Treatment
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
China Medical University Hospital; Surgery
🇨🇳Taichung, Taiwan
Magee-Woman's Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
🇦🇺Bull Creek, Western Australia, Australia
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Univ of Chicago
🇺🇸Chicago, Illinois, United States
Hospital Sao Rafael - HSR
🇧🇷Salvador, BA, Brazil
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
🇪🇸Santiago de Compostela, LA Coruña, Spain
Hospital Universitario Virgen Macarena; Servicio de Oncologia
🇪🇸Sevilla, Spain
Hospital ClÃnico Universitario de Valencia; Servicio de OncologÃa
🇪🇸Valencia, Spain
National Taiwan Uni Hospital; General Surgery
🇨🇳Taipei, Taiwan