To Study the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination with Atezolizumab and Chemotherapy in Patients with Triple-Negative Breast Cancer.
- Conditions
- Triple-Negative Breast CancerMedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 23.0Level: LLTClassification code 10084066Term: Triple negative breast cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000531-47-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
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
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 thatdisease 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method