search
Back to results

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

Primary Purpose

Triple-Negative Breast Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tiragolumab
Atezolizumab
Nab-paclitaxel
Tiragolumab
Atezolizumab
Nab-paclitaxel
Carboplatin
Doxorubicin
Cyclophosphamide
Granulocyte colony-stimulating factor (G-CSF)
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Triple-Negative Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Birmingham
  • Univ of Chicago
  • Levine Cancer Institute
  • Magee-Woman's Hospital
  • Tennessee Onc., PLLC - SCRI
  • Mater Hospital; Cancer Services
  • Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
  • Hospital Sao Rafael - HSR
  • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
  • Hospital Sírio-Libanês
  • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
  • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
  • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
  • Severance Hospital, Yonsei University Health System
  • Seoul National University Hospital
  • Asan Medical Center
  • Arkhangelsk Regional Clinical Oncology Dispensary
  • SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
  • Blokhin Cancer Research Center; Combined Treatment
  • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
  • Hospital Universitario Virgen Macarena; Servicio de Oncologia
  • Hospital Clínico Universitario de Valencia; Servicio de Oncología
  • China Medical University Hospital; Surgery
  • National Taiwan Uni Hospital; General Surgery

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel

Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC

Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Percentage of Participants With Adverse Events (Cohort B)
Confirmed Objective Response Rate ORR (Cohort A)

Secondary Outcome Measures

Percentage of Participants With Adverse Events (Cohort A)
Progression-free Survival (Cohort A)
Duration of Response (Cohort A)
Overall Survival (Cohort A)
Serum Concentrations of Tiragolumab
TD visit: treatment discontinuation visit
Serum Concentrations of Atezolizumab
Plasma Concentrations of Nab-paclitaxel (Cohort B)
Plasma Concentrations of Carboplatin (Cohort B)
Plasma Concentrations of Doxorubicin (Cohort B)
Plasma Concentrations of Cyclophosphamide (Cohort B)
Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
Percentage of Participants With ADAs to Atezolizumab

Full Information

First Posted
October 5, 2020
Last Updated
March 13, 2023
Sponsor
Hoffmann-La Roche
search

1. Study Identification

Unique Protocol Identification Number
NCT04584112
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
September 28, 2020 (Actual)
Primary Completion Date
March 8, 2023 (Actual)
Study Completion Date
March 8, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple-Negative Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
83 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Intervention Description
Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Intervention Description
Tiragolumab 420 mg administered by IV infusion Q2W.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab 840 mg administered by IV infusion Q2W.
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin (area under the concentration-time curve [AUC]: 5 milligrams per milliliter per minute [mg/mL/min]) administered by IV infusion Q3W.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Lipodox, Doxil
Intervention Description
Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide 600 mg/m^2 Q2W administered by IV infusion.
Intervention Type
Drug
Intervention Name(s)
Granulocyte colony-stimulating factor (G-CSF)
Other Intervention Name(s)
filgrastim, pegfilgrastim
Intervention Description
G-CSF support for four doses.
Intervention Type
Drug
Intervention Name(s)
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
Intervention Description
GM-CSF support for four doses.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (Cohort B)
Time Frame
Up to approximately 21 months
Title
Confirmed Objective Response Rate ORR (Cohort A)
Time Frame
Up to approximately 21 months
Secondary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (Cohort A)
Time Frame
Up to approximately 21 months
Title
Progression-free Survival (Cohort A)
Time Frame
Up to approximately 21 months
Title
Duration of Response (Cohort A)
Time Frame
Up to approximately 21 months
Title
Overall Survival (Cohort A)
Time Frame
Up to approximately 21 months
Title
Serum Concentrations of Tiragolumab
Description
TD visit: treatment discontinuation visit
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3300
Country
United States
Facility Name
Univ of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Magee-Woman's Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Tennessee Onc., PLLC - SCRI
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Mater Hospital; Cancer Services
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
City
Bull Creek
State/Province
Western Australia
ZIP/Postal Code
6149
Country
Australia
Facility Name
Hospital Sao Rafael - HSR
City
Salvador
State/Province
BA
ZIP/Postal Code
41253-190
Country
Brazil
Facility Name
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
City
Goiania
State/Province
GO
ZIP/Postal Code
74605-070
Country
Brazil
Facility Name
Hospital Sírio-Libanês
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01308-050
Country
Brazil
Facility Name
Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01317-001
Country
Brazil
Facility Name
Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
City
Essen
ZIP/Postal Code
45136
Country
Germany
Facility Name
Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
003-722
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Arkhangelsk Regional Clinical Oncology Dispensary
City
Arkhangelsk
State/Province
Arhangelsk
ZIP/Postal Code
163045
Country
Russian Federation
Facility Name
SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
City
Moskva
State/Province
Moskovskaja Oblast
ZIP/Postal Code
111123
Country
Russian Federation
Facility Name
Blokhin Cancer Research Center; Combined Treatment
City
Moskva
State/Province
Moskovskaja Oblast
ZIP/Postal Code
115478
Country
Russian Federation
Facility Name
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
City
Santiago de Compostela
State/Province
LA Coruña
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena; Servicio de Oncologia
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia; Servicio de Oncología
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
China Medical University Hospital; Surgery
City
Taichung
ZIP/Postal Code
404
Country
Taiwan
Facility Name
National Taiwan Uni Hospital; General Surgery
City
Taipei
ZIP/Postal Code
100
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Learn more about this trial

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

We'll reach out to this number within 24 hrs