Clinical Trial: NCT04584112 - My Cancer Genome

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

URL:

https://clinicaltrials.gov/show/NCT04584112

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

Drug	Synonyms	Arms
Tiragolumab		Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
Atezolizumab	Tecentriq	Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
Nab-paclitaxel	Abraxane	Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
Tiragolumab		Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Atezolizumab	Tecentriq	Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Nab-paclitaxel	Abraxane	Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Carboplatin		Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC
Doxorubicin	Lipodox, Doxil	Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Cyclophosphamide		Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Granulocyte colony-stimulating factor (G-CSF)	filgrastim, pegfilgrastim	Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Granulocyte-macrophage colony-stimulating factor (GM-CSF)		Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC

Purpose

Trial Arms

Name	Type	Description	Interventions
Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel	Experimental	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.	Tiragolumab Atezolizumab Nab-paclitaxel
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC	Experimental	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.	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-AC	Experimental	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.	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 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

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

August 25, 2021

Clinical Trials /

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