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

Triple-Negative Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04584112
• Other study ID #: CO42177
• Secondary ID: 2020-000531-47
• Status: Completed
• Phase: Phase 1
• Start date: September 28, 2020
• Est. completion date: March 8, 2023

Study information

• Verified date: March 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: March 8, 2023
• Est. primary completion date: March 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Cancer

Intervention

Drug:
• Tiragolumab
Tiragolumab 840 milligrams (mg) administered by intravenous (IV) infusion on Day 1 of every 28-day cycle.
• Atezolizumab
Atezolizumab 1680 mg administered by IV infusion on Day 1 of every 28-day cycle.
• 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.
• Tiragolumab
Tiragolumab 420 mg administered by IV infusion Q2W.
• Atezolizumab
Atezolizumab 840 mg administered by IV infusion Q2W.
• Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
• Carboplatin
Carboplatin (area under the concentration-time curve [AUC]: 5 milligrams per milliliter per minute [mg/mL/min]) administered by IV infusion Q3W.
• Doxorubicin
Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.
• Cyclophosphamide
Cyclophosphamide 600 mg/m^2 Q2W administered by IV infusion.
• Granulocyte colony-stimulating factor (G-CSF)
G-CSF support for four doses.
• Granulocyte-macrophage colony-stimulating factor (GM-CSF)
GM-CSF support for four doses.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Germany,  Korea, Republic of,  Russian Federation,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (Cohort B)		Up to approximately 21 months
Primary	Confirmed Objective Response Rate ORR (Cohort A)		Up to approximately 21 months
Secondary	Percentage of Participants With Adverse Events (Cohort A)		Up to approximately 21 months
Secondary	Progression-free Survival (Cohort A)		Up to approximately 21 months
Secondary	Duration of Response (Cohort A)		Up to approximately 21 months
Secondary	Overall Survival (Cohort A)		Up to approximately 21 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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