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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04584112




Registration number
NCT04584112
Ethics application status
Date submitted
5/10/2020
Date registered
12/10/2020

Titles & IDs
Public title
A Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Participants With Triple-Negative Breast Cancer
Scientific 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
Secondary ID [1] 0 0
2020-000531-47
Secondary ID [2] 0 0
CO42177
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Triple-Negative Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tiragolumab
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Tiragolumab
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Carboplatin
Treatment: Drugs - Doxorubicin
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Granulocyte colony-stimulating factor (G-CSF)
Treatment: Drugs - Granulocyte-macrophage colony-stimulating factor (GM-CSF)

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.

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.

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.


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

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

Treatment: Drugs: 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.

Treatment: Drugs: Tiragolumab
Tiragolumab 420 mg administered by IV infusion Q2W.

Treatment: Drugs: Atezolizumab
Atezolizumab 840 mg administered by IV infusion Q2W.

Treatment: Drugs: Nab-paclitaxel
Nab-paclitaxel 125 mg/m\^2 administered by IV infusion QW.

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

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

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

Treatment: Drugs: Granulocyte colony-stimulating factor (G-CSF)
G-CSF support for four doses.

Treatment: Drugs: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
GM-CSF support for four doses.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events (Cohort B)
Timepoint [1] 0 0
Up to approximately 21 months
Primary outcome [2] 0 0
Confirmed Objective Response Rate ORR (Cohort A)
Timepoint [2] 0 0
Up to approximately 21 months
Secondary outcome [1] 0 0
Percentage of Participants With Adverse Events (Cohort A)
Timepoint [1] 0 0
Up to approximately 21 months
Secondary outcome [2] 0 0
Progression-free Survival (Cohort A)
Timepoint [2] 0 0
Up to approximately 21 months
Secondary outcome [3] 0 0
Duration of Response (Cohort A)
Timepoint [3] 0 0
Up to approximately 21 months
Secondary outcome [4] 0 0
Overall Survival (Cohort A)
Timepoint [4] 0 0
Up to approximately 21 months
Secondary outcome [5] 0 0
Serum Concentrations of Tiragolumab
Timepoint [5] 0 0
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 outcome [6] 0 0
Serum Concentrations of Atezolizumab
Timepoint [6] 0 0
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 outcome [7] 0 0
Plasma Concentrations of Nab-paclitaxel (Cohort B)
Timepoint [7] 0 0
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 outcome [8] 0 0
Plasma Concentrations of Carboplatin (Cohort B)
Timepoint [8] 0 0
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 outcome [9] 0 0
Plasma Concentrations of Doxorubicin (Cohort B)
Timepoint [9] 0 0
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 outcome [10] 0 0
Plasma Concentrations of Cyclophosphamide (Cohort B)
Timepoint [10] 0 0
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 outcome [11] 0 0
Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
Timepoint [11] 0 0
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 outcome [12] 0 0
Percentage of Participants With ADAs to Atezolizumab
Timepoint [12] 0 0
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
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/03/2023
Sample size
Target
Accrual to date
Final
83
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Mater Hospital; Cancer Services - South Brisbane
Recruitment hospital [2] 0 0
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit - Bull Creek
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
6149 - Bull Creek
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
Brazil
State/province [6] 0 0
BA
Country [7] 0 0
Brazil
State/province [7] 0 0
GO
Country [8] 0 0
Brazil
State/province [8] 0 0
SP
Country [9] 0 0
Germany
State/province [9] 0 0
Essen
Country [10] 0 0
Germany
State/province [10] 0 0
Heidelberg
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Russian Federation
State/province [12] 0 0
Arhangelsk
Country [13] 0 0
Russian Federation
State/province [13] 0 0
Moskovskaja Oblast
Country [14] 0 0
Spain
State/province [14] 0 0
LA Coruña
Country [15] 0 0
Spain
State/province [15] 0 0
Sevilla
Country [16] 0 0
Spain
State/province [16] 0 0
Valencia
Country [17] 0 0
Taiwan
State/province [17] 0 0
Taichung
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04584112