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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04584112

Collaborator

(none)

Enrollment

Locations

Arms

26.5

Anticipated Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Triple-Negative Breast Cancer	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)	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 28, 2020

Anticipated Primary Completion Date :

Dec 15, 2022

Anticipated Study Completion Date :

Dec 15, 2022

Arms and Interventions

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
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 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 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.

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

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 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 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.

Outcome Measures

Primary Outcome Measures

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

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]
TD visit: treatment discontinuation visit
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294-3300
2	Univ of Chicago	Chicago	Illinois	United States	60637
3	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
4	Magee-Woman's Hospital	Pittsburgh	Pennsylvania	United States	15213
5	Tennessee Onc., PLLC - SCRI	Nashville	Tennessee	United States	37203
6	Mater Hospital; Cancer Services	South Brisbane	Queensland	Australia	4101
7	Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit	Bull Creek	Western Australia	Australia	6149
8	Hospital Sao Rafael - HSR	Salvador	BA	Brazil	41253-190
9	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO	Brazil	74605-070
10	Hospital Sírio-Libanês	Sao Paulo	SP	Brazil	01308-050
11	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP	Brazil	01317-001
12	Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum	Essen		Germany	45136
13	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg		Germany	69120
14	Seoul National University Hospital	Seoul		Korea, Republic of	03080
15	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
16	Asan Medical Center	Seoul		Korea, Republic of	05505
17	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk	Arhangelsk	Russian Federation	163045
18	SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"	Moskva	Moskovskaja Oblast	Russian Federation	111123
19	Blokhin Cancer Research Center; Combined Treatment	Moskva	Moskovskaja Oblast	Russian Federation	115478
20	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña	Spain	15706
21	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla		Spain	41009
22	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia		Spain	46010
23	China Medical University Hospital; Surgery	Taichung		Taiwan	404
24	National Taiwan Uni Hospital; General Surgery	Taipei		Taiwan	100