Non-small cell lung cancer (NSCLC) with a documented driver mutation (EGFR, ALK, ROS, BRAF, MET, RET, NTRK).
Conditions
Interventions
-Tumor biopsy
-Blood samples and less invasive: urine samples, stool samples and exhaled breath samples
-Atezolizumab/bevacizumab/paclitaxel/carboplatin i.v. treatment as standard of care
-PET/CT scan
Sponsors
University Medical Center Groningen
Eligibility
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated, written informed consent. 2. Female and male subjects aged at least 18 years. 3. Subjects with histologically- or cytologically-documented non squamous NSCLC with a documented driver mutation (such as EGFR, ALK, ROS, BRAF, MET, RET, NTRK1-3, KRAS, NRG1) 4. New (2500/µL -Lymphocyte count =500/µL -Platelet count =100,000/µL (without transfusion) -Hemoglobin =9.0 g/dL. Patients may be transfused or receive erythropoietic treatment to meet this criterion. -AST, ALT, and alkaline phosphatase = 2.5× the upper limit of normal (ULN), with the following exceptions: -Patients with documented liver metastases: AST and/or ALT = 5 × ULN -Patients with documented liver or bone metastases: alkaline phosphatase = 5 × ULN -Serum bilirubin = 1.5 × ULN. Patients with known Gilbert disease who have serum bilirubin level = 3 × ULN may be enrolled. -INR and aPTT = 1.5 × ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose. -Creatinine clearance = 30 mL/min. 10. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: -Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. -Women under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution. -Documentation of irreversible surgical sterilization by hysterectomy, bilateral ophorectomy or bilateral salpingectomy but not tubal ligation. 11. Male subjects should be willing to use barrier contraception
Exclusion criteria
Exclusion criteria: 1. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 14 days prior to inclusion of the study. 2. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies. -Patients who have had prior anti-CTLA-4 treatment may be enrolled, provided the following requirements are met: -Minimum of 6 weeks from the last dose of anti-CTLA-4 -No history of severe immune related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4). 3. CNS disease, treated brain metastases without the need for steroids are allowed. 4. Leptomeningeal disease. 5. Uncontrolled tumor-related pain. -Patients requiring pain medication must be on a stable regimen at study entry. -Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. -Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment. 6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). 7. Malignancies other than NSCLC within 3 years prior with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent). 8. Pregnant and lactating women. 9. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. 10. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cell products or any component of the atezolizumab formulation. 11. History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. -Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. -Patients with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study. 12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. -History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 13. Positive test for HIV. 14. Patients with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. 15. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Predictive value of response to treatment (PFS) by blood test, with emphasis on acquired resistance mechanisms. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Predictive value of response to treatment (PFS) by NGS blood test, with emphasis on acquired resistance mechanisms by the following subgroup of response: -ctDNA profiles associated with primary resistance (PD within 6 mo); -ctDNA profiles associated with acquired resistance (PD 6 mo-24 mo); -ctDNA profiles associated with continuing response of 2 years and more. 2. Predictive value of TMB and clustered Foundation one genes in pretreatment biopsy on OS/continuing response. 3. Predictive value of ctDNA in urine to response to treatment. 4. Predictive value of baseline microbioma to response to treatment. 5. Predictive value of exhaled breath analysis by electronic nose (SpiroNose) to response to treatment. 6. Predictive response of combining different biomarkers together (SpiroNose, microbioma, genes from ctDNA) 7. PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first in total population and EGFR vs Non-EGFR mutation 8. PFS, defined as the time from randomization to the first occurrence of disease progression as determined by ddPCR or death from any cause, whichever occurs first in the total population and EGFR vs Non- EGFR mutation 9. OS, defined as the time from randomization to death from any cause in the total population and EGFR vs Non-EGFR mutation population 10. To determine the impact of treatment as measured by time to deterioration (TTD) in patient-reported lung cancer symptoms of cough, dyspnea (single-item and multi-item subscales), chest pain, or arm/shoulder pain, using the European Organisation for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core (QLQ-C30) and the supplemental lung cancer module (QLQ-LC13) in the EGFR and non-EGFR population 11. To determine the impact of treatment as measured by change from baseline in patient-reported | — |
Contacts
Public ContactThea Scholtens
University Medical Center Groningen
Outcome results
None listed