This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Adequate haematologic and end-organ function
Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
Documented disease progression occurring within 12 months from the last treatment with curative intent
Prior treatment (of early breast cancer) with an anthracycline and taxane
Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
Measurable or non-measurable disease, as defined by RECIST 1.1
Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
Eastern Cooperative Oncology Group performance status 0-1
Life expectancy ≥ 12 weeks
Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening
Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.
Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm
PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

Criterios de exclusión

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 randomisation
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
Symptomatic or rapid visceral progression
No prior treatment with an anthracycline and taxane
History of leptomeningeal disease
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
Uncontrolled tumour-related pain
Uncontrolled or symptomatic hypercalcemia
Malignancies other than TNBC within 5 years prior to randomisation)
Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina
Presence of an abnormal ECG
Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
Current treatment with anti-viral therapy for HBV.
Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
Treatment with investigational therapy within 28 days prior to randomisation
Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
History of autoimmune disease
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo
Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial
Inability to swallow pills
Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine
Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine

Intervenciones

drug

Atezolizumab

Atezolizumab will be administered, 1200 mg by IV infusion with : gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

drug

Placebo

Placebo will be administered, 1200 mg by IV infusion with : gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle or with capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

drug

Gemcitabine

Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

drug

Capecitabine

Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle

drug

Carboplatin

Carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle

A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Atezolizumab

Placebo

Gemcitabine

Capecitabine

Carboplatin

Ubicaciones

Hospital Provincial del Centenario

Instituto de Oncología de Rosario

Patrocinadores