Locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) who have progressed following standard systemic chemotherapy (including if given in combination with anti-PD-1 therapy, after anti-PD-1 as monotherapy, or after tyrosine kinase inhibitor [TKI] therapy). NSCLC
Conditions
Interventions
The investigational medicinal product (IMP) for this study is Atezolizumab (Tecentriq).
TECENTRIQ (atezolizumab) is a humanized immunoglobulin (IgG1) monoclonal antibody that is produced in Chinese hamster ovary (CHO) cells.
Sponsors
F. HOFFMANN-LA ROCHE LTD
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: 1. Signed Informed Consent Form 2. Age = 18 years 3. Able to comply with the study protocol, in the investigator’s judgment 4. Histologically or cytologically documented Stage IIIb or Stage IV NSCLC that has progressed following standard systemic chemotherapy (including if given in combination with anti-PD-1 therapy, after anti-PD-1 as monotherapy, or after TKI therapy). Patients with a previously detected sensitizing EGFR mutation or ALK fusion oncogene must have received targeted therapy (TKI), followed by at least one line of standard systemic chemotherapy, prior to receiving atezolizumab. Overall, patients should not have received more than two lines of standard systemic chemotherapy. Patients who have discontinued first-line or second-line therapy due to intolerance are also eligible – Staging must be according to the UICC/AJCC system, 7th edition (Detterbeck et al. 2009) (see Appendix 8) – Pathological characterization may be conducted on tumor specimens from earlier stage disease, but the tumor samples must be sufficient to distinguish squamous or non-squamous histology – Chemotherapy regimens will be counted based on interval disease progression, and not on the number of agents or the number of switches in agents (e.g., a first-line or second-line therapy that consists of several cycles of a platinum doublet and subsequent maintenance therapy that introduces or switches to a new chemotherapy agent without interval disease progression will all be considered one chemotherapy regimen) – Patients with a previously-detected sensitizing EGFR mutation must have experienced disease progression (during or after treatment) on an EGFR TKI (erlotinib, gefitinib, osimertinib, etc.) – Patients with a previously detected ALK fusion oncogene must have experienced disease progression (during or after treatment) with crizotinib, alectinib, or another ALK inhibitor – Prior radiation therapy is allowed, provided that the patient has recovered from any toxic effects thereof. Combined radiation/chemotherapy treatment constitutes a single regimen – Combined radiation/chemotherapy treatment (chemoradiation) counts as one prior chemotherapy regimen if < 6 months have elapsed between the last dose and the date of recurrence – Adjuvant/neoadjuvant chemotherapy is not counted as a line of treatment – Debulking surgery and anticancer agents used for pleurodesis are not counted as lines of therapy 5. The last dose of prior systemic anticancer therapy must have been administered = 21 days prior to study treatment initiation 6. The last dose of prior anti-PD-1 therapy must have been administered – Nivolumab must have been discontinued = 14 days and pembrolizumab = 21 days prior to study treatment initiation, providing that these treatments were not administered in a clinical trial setting 7. Measurable disease, as defined by Response Evaluation Criteria for Solid Tumors, Version 1.1 (RECIST v1.1) 8. Patients with asymptomatic CNS metastases (treated or untreated), as determined by CT or MRI evaluation during screening and prior radiographic evaluation, are eligible 9. ECOG performance status 0, 1, or 2 [Appendix 7] 10. Life expectancy = 12 weeks 11. Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 2 weeks prior to the first study treatment: – Absolute neutrophil count = 1500 cells/µL (without granulocyte colony-stim
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: 1. Symptomatic CNS metastases 2. 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 study treatment initiation 3. Leptomeningeal disease 4. Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures 5. Pregnant or lactating, or intending to become pregnant during the study – Women who are not postmenopausal (postmenopausal defined as = 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study drug 6. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome) 7. Significant cardiovascular disease, such as New York Heart Association cardiac disease = Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina – Patients with known coronary artery disease or left ventricular ejection fraction 8 weeks – Patients with a history of serious or life threatening immune-related events – No more than 1 concomitant autoimmune disease at the time of study entry is allowed unless one of them is: Autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone Controlled Type I diabetes mellitus on a stable dose of insulin regimen A medical history of such entities as atopic disease or childhood arthralgias, where the clinical suspicion of autoimmune disease is low. In addition, transient autoimmune manifestations of an acute infectious disease that resolved upon treatment of the infectious agent are not excluded (e.g., acute Lyme arthritis) 15. Prior allogeneic stem cell or solid organ transplantation 16. History of idiopathic pulmonary fibrosis, including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e., bronch
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: • To evaluate the long-term safety of atezolizumab in previously treated patients with advanced NSCLC;Timepoints: • Incidence of serious adverse events (SAEs) related to atezolizumab treatment;Measure: • Incidence of immune-related adverse events (irAEs) related to atezolizumab treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: • To further evaluate the efficacy of atezolizumab in previously treated patients with advanced NSCLC;Timepoints: • Duration of response (DOR), ;Measure: defined as the time from initial response to disease progression or death among patients who have experienced a CR or PR (unconfirmed) during the study. Duration of response will be calculated based on disease status evaluated by the investigator according to RECIST v1.1 and also by disease status evaluated by the investigator according to modified RECIST;Name: • To further evaluate the long-term safety and efficacy of atezolizumab in previously treated patients with advanced NSCLC;Timepoints: • Safety and efficacy of atezolizumab in subgroups of the study population differentiated according to: ;Measure: Presence of CNS metastases at baseline (yes vs. no) ECOG performance status (0 or 1 vs. 2) Histologic subtype (squamous vs. non-squamous) History of or current autoimmune disease (yes vs. no) Prior anticancer treatment ;Name: • To further evaluate the long-term safety and efficacy of atezolizumab in previously treated patients with advanced NSCLC;Timepoints: • Progression-free survival from start of new anti-cancer therapy;Measure: defined as the time from initiation of new anti-cancer therapy to objective tumor progression on next-line treatment or death from any cause;Name: • To further evaluate the long-term safety and efficacy of atezolizumab in previously treated patients with advanced NSCLC;Timepoints: • Objective response rate from start of new anti-cancer therapy;Measure: defined as the percentage of patients who attain complete response (CR) or partial response (PR);Name: • To further evaluate the long-term safety and efficacy of atezolizumab in previously treated patients with advanced NSCLC;Timepoints: • Progression-free survival 2 (PFS2), ;Measure: defined as the time from initiation of study treatment to objective tumor progression on next-line treatment or death from any cause;Name: • To evalu | — |
Countries
Argentina, Brazil, China, Colombia, Costa Rica, Denmark, Greece, Guatemala, Italy, Latvia, Lebanon, Malaysia, Mexico, Morocco, Netherlands, Panama, Peru
Contacts
Public ContactFadi ElKarak
Bellevue Medical Center
Outcome results
None listed