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 |
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Recruitment Status :
Completed
First Posted : October 12, 2020
Last Update Posted : March 15, 2023
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Sponsor:
Hoffmann-La Roche
Information provided by (Responsible Party):
Hoffmann-La Roche
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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 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 83 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 |
| Actual Primary Completion Date : | March 8, 2023 |
| Actual Study Completion Date : | March 8, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
Drug Information available for:
Atezolizumab
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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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.
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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. |
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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.
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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 :
- Percentage of Participants With Adverse Events (Cohort B) [ Time Frame: Up to approximately 21 months ]
- Confirmed Objective Response Rate ORR (Cohort A) [ Time Frame: Up to approximately 21 months ]
Secondary Outcome Measures :
- Percentage of Participants With Adverse Events (Cohort A) [ Time Frame: Up to approximately 21 months ]
- Progression-free Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
- Duration of Response (Cohort A) [ Time Frame: Up to approximately 21 months ]
- Overall Survival (Cohort A) [ Time Frame: Up to approximately 21 months ]
- 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
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
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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
Locations
Show 24 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
| Study Director: | Clinical Trial | Hoffmann-La Roche |
| 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: | March 15, 2023 |
| Last Verified: | March 2023 |
| 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). |
| 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 Antibodies, Monoclonal Lenograstim |
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 |