Triple-Negative Breast Cancer MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: LLT Classification code 10084066 Term: Triple negative breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: General Inclusion Criteria (Cohort A and Cohort B): • Age >= 18 years • Eastern Cooperative Oncology Group Performance Status of 0 or 1 • Adequate hematologic and end-organ function • Negative HIV test at screening • Negative hepatitis B surface antigen (HBsAg) test at screening • Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating eggs for at least 5 months after the final dose of atezolizumab, 90 days after the final dose of tiragolumab, 1 month after the final dose of nab-paclitaxel, 6 months after the final dose of carboplatin or doxorubicin, or 12 months after the final dose of cyclophosphamide • For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm for 90 days after the final dose of tiragolumab, or 6 months after the final dose of nab-paclitaxel, carboplatin, doxorubicin, or cyclophosphamide • For women who are not postmenopausal or have undergone a sterilization procedure, a negative serum pregnancy test result is required within 14 days prior to initiation of study treatment. Cancer-Specific Inclusion Criteria for Cohort A (Metastatic TNBC): • Life expectancy >= 12 weeks • Metastatic or locally advanced unresectable, histologically documented TNBC • Only patients with metastatic TNBC tumors that are centrally tested and found to be PD-L1 positive will be enrolled • No prior chemotherapy or targeted systemic therapy for inoperable, locally advanced, or metastatic TNBC • Measurable disease, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors(RECIST), Version 1.1. Cancer-Specific Inclusion Criteria for Cohort B (Early TNBC): • Histologically documented TNBC • Confirmed tumor PD-L1 evaluation as documented through central testing of a representative formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimen in paraffin blocks or at least 20 unstained slides • Primary breast tumor size of > 2 cm on at least one radiographic or clinical measurement • Stage at presentation: cT2-cT4, cN0-cN3, and cM0 • Patient agreement to undergo appropriate surgical management after completion of neoadjuvant treatment • Baseline left ventricular ejection fraction (LVEF) >= 53%, as measured on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 47 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: General Medical Exclusion Criteria (Cohort A and Cohort B): • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment, within 90 days after tiragolumab treatment, within 5 months after atezolizumab treatment, within 6 months after nab-paclitaxel, carboplatin, or doxorubicin treatment, or within 12 months after cyclophosphamide treatment, whichever is longer • Evidence of significant uncontrolled concurrent disease that could affect compliance with the protocol or interpretation of results • Significant cardiovascular disease • Severe infection within 4 weeks prior to initiation of study treatment • Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment • Major surgical procedure within 28 days prior to initiation of study treatment or anticipation of the need for a major surgical procedure during the study other than for diagnosis. General Exclusion Criteria Related to Study Treatment (Cohort A and Cohort B): • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins • Known hypersensitivity or allergy to biopharmaceuticals produced in CHO cells or any component of the tiragolumab or atezolizumab formulation • Active or history of autoimmune disease • Prior allogeneic stem cell or solid organ transplantation • History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on the chest computed tomography (CT) scan at screening • Positive EBV viral capsid antigen (VCA) IgM test at screening • Active tuberculosis • Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation that such a live, attenuated vaccine will be required during the study • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, with an exception of anti-PD-1, or anti-PD-L1 therapeutic antibodies • Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives of the drug prior to initiation of study treatment • Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment, or anticipated requirement for systemic immunosuppressive medications during the study. Cancer-Specific Exclusion Criteria for Cohort A (Metastatic TNBC): • FFPE tumor tissue that is PD-L1 negative • 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 • Uncontrolled pleural effusion, pericardial effusion, or ascites • Uncontrolled tumor-related pain and hypercalcemia • Malignancies other than TNBC within 5 years prior to initiation of study treatment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome • Known hypersensitivity to nab-paclitaxel or to any of its excipients. Exclusion Criteria Specific to Cohort B (Early TNBC): • 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 • History of ductal carcinoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Cohort A (PD-L1-Positive Patients with First-Line Metastatic TNBC): - To investigate the safety and tolerability of tiragolumab combined with atezolizumab and nab-paclitaxel - To investigate the efficacy of tiragolumab combined with atezolizumab and nab-paclitaxel. • Cohort B (Patients with Early TNBC in the Neoadjuvant Setting): - To investigate the safety and tolerability of tiragolumab and atezolizumab + nab-paclitaxel carboplatin, doxorubicin, and cyclophosphamide (nab-pac-carbo-AC) compared with tiragolumab and atezolizumab + nab-paclitaxel, doxorubicin and cyclophosphamide (nab-pac-AC).;Secondary Objective: • Cohort A: To characterize the pharmacokinetics of tiragolumab and atezolizumab • Cohort B: To characterize the pharmacokinetics of tiragolumab, atezolizumab, nab-paclitaxel, carboplatin, and AC • To investigate the immune response to tiragolumab and atezolizumab.;Primary end point(s): 1. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) 2. Confirmed ORR (Cohort A). ;Timepoint(s) of evaluation of this end point: 1-2. Approximately 21 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free survival (Cohort A) 2. Duration of response (Cohort A) 3. Overall survival (Cohort A) 4. Serum concentrations of tiragolumab and atezolizumab at specified timepoints (Cohort A) 5. Serum concentrations of tiragolumab and atezolizumab, and plasma concentrations of nab-paclitaxel, carboplatin, and AC at specified timepoints (Cohort B) 6. Prevalence of anti-drug antibody (ADAs) to tiragolumab at baseline and incidence of ADAs to tiragolumab during the study 7. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study.;Timepoint(s) of evaluation of this end point: 1-3. Approximately 21 months 4. Day 1 of Cycle 1, 2, 3, 4, 8, 12, and 16 and at treatment discontinuation visit (Cohort A) 5. Day 1 of Cycle 1-5, and at treatment discontinuation visit (Cohort B) 6-7. At Baseline (Day 1), Day 1 of Cycle 1, 2, 3, 4, 8, 12, and 16 and at treatment discontinuation visit (Cohort A); Day 1 of Cycle 1-5 and at treatment discontinuation (Cohort B). | — |
Countries
Australia, Brazil, Germany, Italy, Korea, Republic of, Russian Federation, Spain, Taiwan, United States
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
Outcome results
None listed