Advanced or metastatic triple-negative breast cancer MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate for concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Other descriptive name: ATEZOLIZUMAB
Concentration unit: mg/ml millig
Sponsors
Medica Scientia Innovation Research (MedSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form (ICF) prior to participation in any study-related activities 2. Male or female patients = 18 years at the time of signing ICF 3. Ability to comply with the study protocol, in the investigator's judgment 4. Histologically confirmed TNBC –regardless of PD-L1 status– per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria based on local testing on the most recent analyzed biopsy. Triple-negative is defined as 3.0 x 109/L; ii. Absolute neutrophil count (ANC) > 1.5 X 109/L; iii. Lymphocyte count 0.5 x 109/L (500L); iv. Platelet count 75.0 x 109/L; v. Hemoglobin > 9.0 g/dL b. Hepatic: Bilirubin = 1.5 times the upper limit of normal (× ULN) (= 3 x ULN in the case of Gilbert’s disease); aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 × ULN (in the case of liver metastases = 5 × ULN); alkaline phosphatase (ALP) = 2.5 × ULN (= 5 × ULN in the case of liver and/or bone metastases). c. Serum albumin = 2.5 g/dL d. Renal: Serum creatinine ULN by urinalysis, proteinuria should be less than 500 mg by 24-hour urine collection. e. Coagulation: - For patients not receiving therapeutic anticoagulation: Partial Thromboplastin Time
Exclusion criteria
Exclusion criteria: 1. Known active uncontrolled or symptomatic central nervous system (CNS) metastases as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases are eligible if they meet the following criteria: • Evidence of measurable disease or non-measurable disease as per RECIST v.1.1. • The patient has no history of intracranial hemorrhage. • The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment. • The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted. 2. History of leptomeningeal disease. 3. Uncontrolled tumor-related pain. 4. Active or history of autoimmune disease or immune deficiency 5. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures. Note: Patients with indwelling catheters (e.g., PleurX®) are allowed. 6. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L; calcium > 12 mg/dL). 7. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. 8. Active tuberculosis. 9. Significant cardiovascular disease 6 months prior to initiation of study treatment. These include New York Heart Association Class II or greater cardiac disease, myocardial infarction, unstable arrhythmia, or unstable angina, symptomatic pericarditis, ventricular arrhythmias –except for benign premature ventricular contractions–, arrhythmias or conduction abnormalities requiring a pacemaker or not controlled with medication, and prior peripheral vascular disease including any cerebrovascular accident including transient ischemic attack, any pulmonary embolism, any prior deep vein thrombosis, and/or any grade = 2 peripheral vascular disease. 10. Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO). 11. Uncontrolled hypertension (systolic blood pressure greater than 160 mmHg and diastolic blood pressure greater than 100 mmHg). 12. Major surgical procedure (defined as requiring general anesthesia) or significant traumatic injury within 28 days of start of study drug, or patients who have not recovered from the side effects of any major surgery. 13. Concurrent malignancy(ies) or malignancy(ies) within 5 years of study enrollment except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required. 14. Treatment with therapeutic oral or IV antibiotics or severe infection 2 weeks prior to initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study. 15. Prior allogeneic stem cell or solid organ transplantation 16. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizuma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy –in terms of progression-free survival (PFS)– of first line atezolizumab in combination with paclitaxel and bevacizumab (Avastin®) in patients with unresectable locally advanced or metastatic TNBC.;Secondary Objective: Efficacy To assess the efficacy –in terms of time to response (TTR), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DoR), overall survival (OS), and best percentage of change in target tumor lesions– of first-line atezolizumab in combination with paclitaxel and bevacizumab (Avastin®) in these patients. Safety To evaluate the safety and tolerability of the addition of atezolizumab to the combination of paclitaxel and bevacizumab (Avastin®) in these patients. Exploratory objectives: • To assess the efficacy of first-line atezolizumab in combination with paclitaxel and bevacizumab (Avastin®) based on Immune-Related RECIST (irRECIST). • To evaluate predictive or prognostic biomarkers associated with disease activity status or response to treatment. • To identify possible mechanisms of resistance to study treatment through the comparative analysis of potential biomarkers from paired pre-treatment and post-progression tumor and/or blood samples.;Primary end point(s): Median PFS, defined as the period of time from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1.;Timepoint(s) of evaluation of this end point: Analysis will be performed on full analysis and per-protocol sets. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy • TTR, defined as the time from the treatment initiation to time of the first objective tumor response (tumor shrinkage of = 30%) observed for patients who achieved a complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1. • ORR, defined as the sum of CR and PR as determined locally by the investigator using RECIST v.1.1. • CBR, defined as the sum of objective responses (CR or PR), or stable disease (SD) for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1. • DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined locally by the investigator using RECIST v.1.1. • OS, defined as the time from treatment initiation to death from any cause or last patient contact. • Best percentage of change from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase in case of no observed increase, as determined locally by the investigator using RECIST v.1.1. Safety Incidence and severity of adverse events (AEs), serious adverse events (SAEs) according to the National Cancer Institute’s – Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0, including dose reductions, delays, and treatment discontinuations. Exploratory endpoints • Immune-related PFS (irPFS) and immune-related ORR (irORR) based on investigator assessment using irRECIST. • Relationship between tumor- and/or immune-related biomarkers and treatment efficacy (PD-L1 expression and tumor-infiltrating lymphocytes [TILs]; mutational tumor load; cytokine profiling; etc.). • Changes in mutation and copy number in oncogenes, tumor suppressors, and/or other genes associated with disease progression assessed in liquid biopsy and/or tumor samples.;Timepoint(s) of evaluation of this end point: Analysis will be performed on full analysis and per-pro | — |
Countries
France, Germany, Italy, Portugal, Spain, United Kingdom
Contacts
Public ContactSusana Vitorino
Medica Scientia Innovation Research (MedSIR)
Outcome results
None listed