Metastatic Triple-negative PD-L1 positive breast cancer MedDRA version: 20.0 Level: PT Classification code 10073100 Term: Metaplastic breast carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Atezolizumab
Product Code: [RO554-1267]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: atezolizumab
CAS Number: 1380723-44-3
Current Sponsor code: RO554-
Sponsors
CONSORZIO ONCOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form 2. Women or men aged =18 years 3. Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic disease 4. Hormone receptor-negative (ER and PgR < 10%) and HER2-negative (IHC 0,1+ or 2+ ISH not amplified) breast cancer, based on the status of the primary tumor and/or the biopsy of metastatic disease before starting first-line therapy and assessed by local laboratory. 5. PD-L1 positive defined as expression on tumor-infiltrating immune cells =1% (SP142 PD-L1 immunohistochemical assay, Ventana Medical Systems), based on the status of the primary tumor and/or the biopsy of metastatic disease before starting first-line therapy and assessed by local laboratory 6. Availability of a representative tumor specimen for translational research 7. Eligible for first-line taxane and carboplatin chemotherapy 8. No prior chemotherapy or targeted systemic therapy (including endocrine therapy) for inoperable locally advanced or metastatic TNBC. Prior radiation therapy for metastatic disease is permitted. There is no required minimum washout period for radiation therapy; however, patients should have recovered from the effects of radiation before enrollment 9. Previous chemotherapy with taxanes and/or carboplatin for early breast cancer (neoadjuvant or adjuvant setting) is permitted if completed =12 months before study entry 10. Previous therapy with immune checkpoint inhibitors for early breast cancer (neoadjuvant or adjuvant setting) is permitted if completed =12 months before study entry 11. ECOG performance status of 0 or 1 12. Life expectancy = 12 weeks 13. Measurable or evaluable disease as defined by RECIST v1.1. 14. Adequate hematologic and end-organ function, defined by laboratory results obtained within 2 weeks prior to the first study treatment (Cycle 1, Day 1) 15. Negative human immunodeficiency virus (HIV) test at screening 16. Negative hepatitis B surface antigen (HBsAg) test at screening 17. 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 positive HBcAb test 18. Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test 19. Women of child bearing potential must agree to either use a contraceptive method with a failure rate of = 1% per year or to remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 5 months after the last dose of atezolizumab, or for at least 6 months after the last dose of paclitaxel. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of = 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic a
Exclusion criteria
Exclusion criteria: 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 at least 2 weeks prior to enrollment. 2. Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met: 3. Uncontrolled pleural effusion, pericardial effusion, or ascites 4. Uncontrolled tumor-related pain 5. Uncontrolled hypercalcemia (>1.5 mmol/L [>6 mg/dL] ionized calcium or serum calcium [uncorrected for albumin] >3 mmol/L [>12 mg/dL] or corrected serum calcium >ULN) or clinically significant (symptomatic) hypercalcemia 6. Malignancies other than TNBC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome 7. Pregnant or lactating women, or intending to become pregnant during the study 8. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) 9. Significant cardiovascular disease 10. Presence of an abnormal ECG that is clinically significant in the investigator’s opinion, including complete left bundle branch block, second- or third degree heart block, evidence of prior myocardial infarction, or QT interval corrected using Fridericia’s formula (QTcF) >470 ms demonstrated by at least two consecutive ECGs 11. Serious infection requiring antibiotics within 2 weeks prior to enrollment, including but not limited to infections requiring hospitalisation or IV antibiotics, such as bacteremia, or severe pneumonia 12. Major surgical procedure within 4 weeks prior to enrollment or anticipation of the need for a major surgical procedure during the study other than for diagnosis 13. Treatment with investigational therapy within 30 days prior to initiation of study treatment 14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the atezolizumab formulation 16. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis,LES,RA, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis (MS), vasculitis, or glomerulonephritis 17. Prior allogeneic stem cell or solid organ transplantation 18. History of idiopathic pulmonary fibrosis (IPF, including pneumonitis), drug-induced pneumonitis, organizing pneumonia 19. Positive test for human immunodeficiency virus (HIV) 20. Active hepatitis B (positive hepatitis B surface antigen [HBsAg] test or hepatitis B virus [HBV] DNA polymerase chain reaction [PCR] test at screening) or hepatitis C (positive hepatitis C virus antibody test at screening). Note: 21. Current treatment with anti-viral therapy for HBV 22. Active tuberculosis 23. Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment or anticipation that such a live, attenuated vaccine will be required during the study 24. Treatment with systemic immunostimulatory agents within 4 weeks or fiv
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients as evaluated by % 2years OS.;Secondary Objective: •To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in terms of % OS at 2.5 years •To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in terms of % OS at 2 years in hormonal receptor (HR) between 1% and 10% •To provide preliminary evidence on the efficacy of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in terms of post-progression survival •To assess the activity of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in terms of ORR, and time to treatment failure •To assess the safety of atezolizumab plus carboplatin plus paclitaxel as first-line therapy in metastatic triple-negative PD-L1 positive breast cancer patients;Primary end point(s): % Overall survival at 2 years;Timepoint(s) of evaluation of this end point: 2 years from last patient enrolled | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Incidence and severity of adverse events and serious adverse events; OS in HR <1% and in HR 1-10%; Post-progression survival; Time to treatment failure; % Overall survival at 2,5 years; Objective response rate;Timepoint(s) of evaluation of this end point: continuosly during the study; 2 years from last patient enrolled; during the study every 12 weeks (± 1 week) starting from day 1; during the study every 12 weeks (± 1 week) starting from day 1; 2.5 years from last patient enrolled; during the study every 12 weeks (± 1 week) starting from day 1 | — |
Countries
Italy
Contacts
Public ContactProject management
Clinical Research Technology Srl
Outcome results
None listed