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

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ClinicalTrials.gov Identifier: NCT04584112
Recruitment Status : Recruiting
First Posted : October 12, 2020
Last Update Posted : November 4, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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: Carboplatin Drug: Doxorubicin Drug: Cyclophosphamide Drug: Granulocyte colony-stimulating factor (G-CSF) Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : September 28, 2020
Estimated Primary Completion Date : March 15, 2022
Estimated Study Completion Date : March 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: 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 Name: 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 Name: Tecentriq

Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
Other Name: 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 Name: 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 Name: 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 Name: Tecentriq

Drug: Nab-paclitaxel
Nab-paclitaxel 125 mg/m^2 administered by IV infusion QW.
Other Name: Abraxane

Drug: Doxorubicin
Doxorubicin 60 mg/m^2 Q2W administered by IV infusion.
Other Name: 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 Name: filgrastim, pegfilgrastim

Drug: Granulocyte-macrophage colony-stimulating factor (GM-CSF)
GM-CSF support for four doses.




Primary Outcome Measures :
  1. Percentage of Participants With Adverse Events (Cohort B) [ Time Frame: Up to approximately 21 months ]
  2. Confirmed Objective Response Rate ORR (Cohort A) [ Time Frame: Up to approximately 21 months ]

Secondary Outcome Measures :
  1. Percentage of Participants With Adverse Events (Cohort A) [ Time Frame: Up to approximately 21 months ]
  2. Progression-free Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
  3. Duration of Response (Cohort A) [ Time Frame: Up to approximately 21 months ]
  4. Overall Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
  5. Serum Concentrations of Tiragolumab [ Time Frame: 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

  6. Serum Concentrations of Atezolizumab [ Time Frame: 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 ]
  7. Plasma Concentrations of Nab-paclitaxel (Cohort B) [ Time Frame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months ]
  8. Plasma Concentrations of Carboplatin (Cohort B) [ Time Frame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months ]
  9. Plasma Concentrations of Doxorubicin (Cohort B) [ Time Frame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months ]
  10. Plasma Concentrations of Cyclophosphamide (Cohort B) [ Time Frame: Cohort B: Day 1 of Cycles (cycle=28 days) 1-5 and at TD visit from start of treatment up to approximately 5 months ]
  11. Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: 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 ]
  12. Percentage of Participants With ADAs to Atezolizumab [ Time Frame: 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04584112


Contacts
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Contact: Reference Study ID Number: CO42177 https://forpatients.roche.com/ 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
Show Show 26 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trial Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04584112    
Other Study ID Numbers: CO42177
2020-000531-47 ( EudraCT Number )
First Posted: October 12, 2020    Key Record Dates
Last Update Posted: November 4, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Doxorubicin
Atezolizumab
Molgramostim
Lenograstim
Antibodies, Monoclonal
Sargramostim
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic