NCT04584112

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).

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
83

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2020

Typical duration for phase_1

Geographic Reach
8 countries

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 28, 2020

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

October 5, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 12, 2020

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 8, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 8, 2023

Completed
Last Updated

March 15, 2023

Status Verified

March 1, 2023

Enrollment Period

2.4 years

First QC Date

October 5, 2020

Last Update Submit

March 13, 2023

Conditions

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (12)

  • Percentage of Participants With Adverse Events (Cohort A)

    Up to approximately 21 months

  • Progression-free Survival (Cohort A)

    Up to approximately 21 months

  • Duration of Response (Cohort A)

    Up to approximately 21 months

  • Overall Survival (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

  • +7 more secondary outcomes

Study Arms (3)

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.

Drug: TiragolumabDrug: AtezolizumabDrug: 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.

Drug: TiragolumabDrug: AtezolizumabDrug: Nab-paclitaxelDrug: CarboplatinDrug: DoxorubicinDrug: CyclophosphamideDrug: Granulocyte colony-stimulating factor (G-CSF)Drug: 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.

Drug: TiragolumabDrug: AtezolizumabDrug: Nab-paclitaxelDrug: DoxorubicinDrug: CyclophosphamideDrug: Granulocyte colony-stimulating factor (G-CSF)Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)

Interventions

Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.

Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel

Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.

Also known as: Tecentriq
Cohort A: Tiragolumab and Atezolizumab + 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.

Also known as: Abraxane
Cohort A: Tiragolumab and Atezolizumab + Nab-paclitaxel

Carboplatin (area under the concentration-time curve \[AUC\]: 5 milligrams per milliliter per minute \[mg/mL/min\]) administered by IV infusion Q3W.

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

Doxorubicin 60 mg/m\^2 Q2W administered by IV infusion.

Also known as: Lipodox, Doxil
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-ACCohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC

Cyclophosphamide 600 mg/m\^2 Q2W administered by IV infusion.

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

G-CSF support for four doses.

Also known as: filgrastim, pegfilgrastim
Cohort B: Tiragolumab and Atezolizumab + Nab-pac-ACCohort B: Tiragolumab and Atezolizumab + Nab-pac-carbo-AC

GM-CSF support for four doses.

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300, United States

Location

Univ of Chicago

Chicago, Illinois, 60637, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Magee-Woman's Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Tennessee Onc., PLLC - SCRI

Nashville, Tennessee, 37203, United States

Location

Mater Hospital; Cancer Services

South Brisbane, Queensland, 4101, Australia

Location

Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit

Bull Creek, Western Australia, 6149, Australia

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital Araujo Jorge; Departamento de Ginecologia E Mama

Goiânia, Goiás, 74605-070, Brazil

Location

Hospital Sírio-Libanês

São Paulo, São Paulo, 01308-050, Brazil

Location

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo, 01317-001, Brazil

Location

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum

Essen, 45136, Germany

Location

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Arkhangelsk Regional Clinical Oncology Dispensary

Arkhangelsk, Arhangelsk, 163045, Russia

Location

SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"

Moskva, Moscow Oblast, 111123, Russia

Location

Blokhin Cancer Research Center; Combined Treatment

Moskva, Moscow Oblast, 115478, Russia

Location

Severance Hospital, Yonsei University Health System

Seoul, 003-722, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

Hospital Clínico Universitario de Valencia; Servicio de Oncología

Valencia, 46010, Spain

Location

China Medical University Hospital; Surgery

Taichung, 404, Taiwan

Location

National Taiwan Uni Hospital; General Surgery

Taipei, 100, Taiwan

Location

Related Publications (1)

  • Kuemmel S, Jung KH, Andrade L, Assad-Suzuki D, de la Cruz Merino L, Freitas-Junior R, Hegg R, Huang CS, Martin H, Schneeweiss A, Dieterich M, Nguyen Duc A, Feng Y, Meng R, Swat A, Seiller A, Bermejo B, Hamilton EP. Safety and efficacy of tiragolumab, atezolizumab and chemotherapy for early-stage or PD-L1-positive advanced triple-negative breast cancer: a phase Ib study. ESMO Open. 2025 Dec;10(12):105869. doi: 10.1016/j.esmoop.2025.105869. Epub 2025 Nov 25.

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Tiragolumabatezolizumab130-nm albumin-bound paclitaxelAlbumin-Bound PaclitaxelCarboplatinDoxorubicinliposomal doxorubicinCyclophosphamideGranulocyte Colony-Stimulating FactorFilgrastimpegfilgrastimGranulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Breast NeoplasmsNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

PaclitaxelTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesAlbuminsProteinsAmino Acids, Peptides, and ProteinsCoordination ComplexesDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsColony-Stimulating FactorsGlycoproteinsGlycoconjugatesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological Factors

Study Officials

  • Clinical Trial

    Hoffmann-La Roche

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 5, 2020

First Posted

October 12, 2020

Study Start

September 28, 2020

Primary Completion

March 8, 2023

Study Completion

March 8, 2023

Last Updated

March 15, 2023

Record last verified: 2023-03

Data Sharing

IPD Sharing
Will share

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).

Locations