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

March 13, 2023 updated by: Hoffmann-La Roche

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
83

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Hospital; Cancer Services
    • Western Australia
      • Bull Creek, Western Australia, Australia, 6149
        • Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
  • Brazil
    • BA
      • Salvador, BA, Brazil, 41253-190
        • Hospital Sao Rafael - HSR
    • GO
      • Goiania, GO, Brazil, 74605-070
        • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
    • SP
      • Sao Paulo, SP, Brazil, 01317-001
        • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
      • Sao Paulo, SP, Brazil, 01308-050
        • Hospital Sírio-Libanês
  • Germany
      • Essen, Germany, 45136
        • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
      • Heidelberg, Germany, 69120
        • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 003-722
        • Severance Hospital, Yonsei University Health System
  • Russian Federation
    • Arhangelsk
      • Arkhangelsk, Arhangelsk, Russian Federation, 163045
        • Arkhangelsk Regional Clinical Oncology Dispensary
    • Moskovskaja Oblast
      • Moskva, Moskovskaja Oblast, Russian Federation, 111123
        • SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
      • Moskva, Moskovskaja Oblast, Russian Federation, 115478
        • Blokhin Cancer Research Center; Combined Treatment
  • Spain
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena; Servicio de Oncologia
      • Valencia, Spain, 46010
        • Hospital Clínico Universitario de Valencia; Servicio de Oncología
    • LA Coruña
      • Santiago de Compostela, LA Coruña, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
  • Taiwan
      • Taichung, Taiwan, 404
        • China Medical University Hospital; Surgery
      • Taipei, Taiwan, 100
        • National Taiwan Uni Hospital; General Surgery
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-3300
        • University of Alabama at Birmingham
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Univ of Chicago
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Levine Cancer Institute
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee-Woman's Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Onc., PLLC - SCRI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort A: Tiragolumab and Atezolizumab + 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.
Drug: Tiragolumab
Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.
Drug: Atezolizumab
Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Nab-paclitaxel
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.
Other Names:
  • Abraxane
Drug: Tiragolumab
Tiragolumab 420 mg administered by IV infusion Q2W.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion Q2W.
Other Names:
  • Tecentriq
Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
Other Names:
  • Abraxane
Experimental: Cohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC
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.
Drug: Tiragolumab
Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.
Drug: Atezolizumab
Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Nab-paclitaxel
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.
Other Names:
  • Abraxane
Drug: Tiragolumab
Tiragolumab 420 mg administered by IV infusion Q2W.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion Q2W.
Other Names:
  • Tecentriq
Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
Other Names:
  • Abraxane
Drug: Carboplatin
Carboplatin (area under the concentration-time curve [AUC]: 5 milligrams per milliliter per minute [mg/mL/min]) administered by IV infusion Q3W.
Drug: Doxorubicin
Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.
Other Names:
  • Lipodox, Doxil
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m^2 Q2W administered by IV infusion.
Drug: Granulocyte colony-stimulating factor (G-CSF)
G-CSF support for four doses.
Other Names:
  • filgrastim, pegfilgrastim
Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
GM-CSF support for four doses.
Experimental: Cohort B: Tiragolumab and Atezolizumab + Nab-pac-AC
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.
Drug: Tiragolumab
Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.
Drug: Atezolizumab
Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.
Other Names:
  • Tecentriq
Drug: Nab-paclitaxel
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.
Other Names:
  • Abraxane
Drug: Tiragolumab
Tiragolumab 420 mg administered by IV infusion Q2W.
Drug: Atezolizumab
Atezolizumab 840 mg administered by IV infusion Q2W.
Other Names:
  • Tecentriq
Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
Other Names:
  • Abraxane
Drug: Doxorubicin
Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.
Other Names:
  • Lipodox, Doxil
Drug: Cyclophosphamide
Cyclophosphamide 600 mg/m^2 Q2W administered by IV infusion.
Drug: Granulocyte colony-stimulating factor (G-CSF)
G-CSF support for four doses.
Other Names:
  • filgrastim, pegfilgrastim
Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
GM-CSF support for four doses.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of Participants With Adverse Events (Cohort B)
Time Frame: Up to approximately 21 months
Up to approximately 21 months
Confirmed Objective Response Rate ORR (Cohort A)
Time Frame: Up to approximately 21 months
Up to approximately 21 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Adverse Events (Cohort A)
Time Frame: Up to approximately 21 months
Up to approximately 21 months
Progression-free Survival (Cohort A)
Time Frame: Up to approximately 21 months
Up to approximately 21 months
Duration of Response (Cohort A)
Time Frame: Up to approximately 21 months
Up to approximately 21 months
Overall Survival (Cohort A)
Time Frame: Up to approximately 21 months
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 28, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 8, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 8, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 5, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 15, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CO42177
  • 2020-000531-47 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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).

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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