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

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: Completed
• Conditions: Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: Tiragolumab; Drug: Atezolizumab; Drug: Nab-paclitaxel; Drug: Tiragolumab; Drug: Atezolizumab; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Granulocyte colony-stimulating factor (G-CSF); Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

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 Sirio-Libanes
• 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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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		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)		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)		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)		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)		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		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		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

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2020
• Primary Completion (Actual): March 8, 2023
• Study Completion (Actual): March 8, 2023

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 12, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Cyclophosphamide; Carboplatin; Paclitaxel; Lenograstim; Albumin-Bound Paclitaxel; Doxorubicin; Antibodies, Monoclonal; Sargramostim; Atezolizumab; Molgramostim
• Other Study ID 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