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

NCT04584112

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CO42177
  • SECONDARY ID: 2020-000531-47
  • NCT ID: NCT04584112

Conditions

  • Triple-Negative Breast Cancer

Interventions

DrugSynonymsArms
TiragolumabCohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
AtezolizumabTecentriqCohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
Nab-paclitaxelAbraxaneCohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
TiragolumabCohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
AtezolizumabTecentriqCohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Nab-paclitaxelAbraxaneCohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
CarboplatinCohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC
DoxorubicinLipodox, DoxilCohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
CyclophosphamideCohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Granulocyte colony-stimulating factor (G-CSF)filgrastim, pegfilgrastimCohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Granulocyte-macrophage colony-stimulating factor (GM-CSF)Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxelExperimentalParticipants 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.
  • Tiragolumab
  • Atezolizumab
  • Nab-paclitaxel
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-ACExperimentalParticipants 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 cycles.
  • Tiragolumab
  • Atezolizumab
  • Nab-paclitaxel
  • Carboplatin
  • Doxorubicin
  • Cyclophosphamide
  • Granulocyte colony-stimulating factor (G-CSF)
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF)
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-ACExperimentalParticipantswith 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 cycles.
  • Tiragolumab
  • Atezolizumab
  • Nab-paclitaxel
  • Doxorubicin
  • Cyclophosphamide
  • Granulocyte colony-stimulating factor (G-CSF)
  • Granulocyte-macrophage colony-stimulating factor (GM-CSF)

Eligibility 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

        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 great 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

          -  History of ductal carcinoma in situ (DCIS), except for patients treated exclusively
             with mastectomy >5 years prior to diagnosis of current breast cancer

          -  History of pleomorphic lobular carcinoma in situ (LCIS), except for patients
             surgically managed >5 years prior to diagnosis of current breast cancer

          -  Synchronous, bilateral invasive breast cancer

          -  Cardiopulmonary dysfunction
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Adverse Events (Cohort B)
Time Frame:Up to approximately 21 months
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

October 9, 2020