Clinical trial NCT04584112: A Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Participants With Triple-Negative Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Triple-Negative Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-10-12
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events (Cohort B)
timeFrame: Up to approximately 21 months
measure: Confirmed Objective Response Rate ORR (Cohort A)
timeFrame: Up to approximately 21 months
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (Cohort A)
timeFrame: Up to approximately 21 months
measure: Progression-free Survival (Cohort A)
timeFrame: Up to approximately 21 months
measure: Duration of Response (Cohort A)
timeFrame: Up to approximately 21 months
measure: Overall Survival (Cohort A)
timeFrame: Up to approximately 21 months
measure: Serum Concentrations of Tiragolumab
timeFrame: 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
measure: Serum Concentrations of Atezolizumab
timeFrame: 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
measure: Plasma Concentrations of Nab-paclitaxel (Cohort B)
timeFrame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months
measure: Plasma Concentrations of Carboplatin (Cohort B)
timeFrame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months
measure: Plasma Concentrations of Doxorubicin (Cohort B)
timeFrame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months
measure: Plasma Concentrations of Cyclophosphamide (Cohort B)
timeFrame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months
measure: Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
timeFrame: 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
measure: Percentage of Participants With ADAs to Atezolizumab
timeFrame: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chicago
country: United States
facility: Univ of Chicago
state: Illinois
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Pittsburgh
country: United States
facility: Magee-Woman's Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Onc., PLLC - SCRI
state: Tennessee
city: South Brisbane
country: Australia
facility: Mater Hospital; Cancer Services
state: Queensland
city: Bull Creek
country: Australia
facility: Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
state: Western Australia
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: BA
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge; Departamento de Ginecologia E Mama
state: GO
city: Sao Paulo
country: Brazil
facility: Hospital Sírio-Libanês
state: SP
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
state: SP
city: Essen
country: Germany
facility: Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Dispensary
state: Arhangelsk
city: Moskva
country: Russian Federation
facility: SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: Blokhin Cancer Research Center; Combined Treatment
state: Moskovskaja Oblast
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia; Servicio de Oncología
city: Taichung
country: Taiwan
facility: China Medical University Hospital; Surgery
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; General Surgery
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trial
role: STUDY_DIRECTOR
References: