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This phase II trial is studying blood and tumor tissue from patients with advanced non-small cell lung cancer who are treated with nivolumab to better understand how nivolumab works. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread by turning on the immune system (T cells). We want to study the effects of nivolumab on the immune system (T cells) by collecting blood samples and samples from patients' tumors.
Full description
PRIMARY OBJECTIVE:
I. To study the sustained proliferation of programmed cell death protein (PD)-1+Ki-67+cluster of differentiation(CD)8 T cells as a predictive biomarker of response to nivolumab by comparing the response rates to nivolumab treatment between two groups of patients (positive vs negative) stratified by the status of PD-1+Ki-67+CD8 T cells.
SECONDARY OBJECTIVES:
I. Characterize phenotype of proliferating T cells in peripheral blood in the setting of nivolumab therapy.
II. Perform gene expression profiling of activated T cells from peripheral blood.
III. Perform T cell receptor (TCR) sequencing of activated T cells from peripheral blood and tumor infiltrating T cells (TILs).
IV. Assess pre-treatment biopsies and biopsies at the time of disease progression for tumor infiltrating lymphocytes.
V. Determine progression free survival (PFS) and overall survival (OS).
OUTLINE:
Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 2 weeks in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days and then every 3 months for up to 3 years.
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Inclusion criteria
Subjects must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent form in accordance with regulatory and institutional guidelines; this must be obtained before the performance of any protocol related procedures that are not part of normal subject care
Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
Histologically confirmed stage IV or recurrent non-small cell lung cancer (NSCLC) per the 7th International Association for the Study of Lung Cancer classification with squamous or non-squamous histology
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2; patients with PS 2 are being included as the primary endpoint of the study is correlation of blood based biomarkers with response; nivolumab is currently approved for both squamous and non-squamous NSCLC
Disease progression following frontline platinum doublet therapy given for metastatic or recurrent disease; there is no restriction on prior lines of therapy following receipt of initial platinum doublet therapy
Prior systemic chemotherapy or other investigational therapy must have been completed at least two weeks prior to administration of nivolumab
Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Subject willing to undergo biopsy prior to treatment with investigational therapy for fresh tissue immune cell analysis and would consider biopsy at disease progression (progression biopsy is not mandated); biopsy should be obtained with core needle; fine needle aspirates are not sufficient; if prior archival tissue is available, it should be submitted
Prior palliative radiotherapy must have been completed at least 2 weeks prior to registration; subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of randomization are strongly encouraged to receive palliative radiotherapy prior to randomization
White blood cell (WBC) ≥ 2000/µL
Neutrophils ≥ 1500/µL
Platelets ≥ 100 x 10³/µL
Hemoglobin > 9.0 g/dL
Serum creatinine ≤ 2 x upper limit of normal (ULN) or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x ULN
Total bilirubin ≤ 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)
Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception; WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab
Women must not be breastfeeding
Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product; women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception
Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy; investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception; highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly
At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below:
HIGHLY EFFECTIVE METHODS OF CONTRACEPTION
LESS EFFECTIVE METHODS OF CONTRACEPTION
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Data sourced from clinicaltrials.gov
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