[18F]-AraG for the Detection of T-Cell Activation in Advanced Non-small Cell Lung Cancer Patients Undergoing PD-1/PD-L1-Directed Therapy

Study Overview
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Brief Summary
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This trial studies how well [18F]-AraG works in detecting T-cell activation in patients with non-small cell lung cancer that has spread to other places in the body (advanced), who are undergoing PD-1/PD-L1-directed therapy. [18F]-AraG is a radiotracer which attaches to immune cells directed at the cancer and shines a light that can be seen using a special camera, called a positron emission tomography or PET scanner. [18F]-AraG may improve the ability to detect a response of the cancer in the body to immunotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To quantify fluorine F 18 Ara-G ([18F]-AraG) uptake (standardized uptake value [SUV]) in advanced non-small cell lung cancer (NSCLC) tumor (primary, nodal, and metastatic sites) at baseline and after 1 dose of anti-PD-1/PD-L1 therapy in both patients treated with PD-1/PD-L1 monotherapy and in patients treated with immunotherapy/chemotherapy combination therapy. II. To correlate change in [18F]-AraG uptake before and after the start of therapy with radiographic response in patients treated with immunotherapy. OUTLINE: Patients receive [18F]-AraG intravenously (IV) and then undergo PET/CT over 2 hours at baseline and within 2 weeks after starting immunotherapy. Patients may also undergo blood sample collection. After completion of study treatment, patients are followed for up to 12 months.

Official Title
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Imaging of T-Cell Activation With [18F]-AraG in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Undergoing PD-1/PD-L1-Directed Therapy

Conditions
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Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, Stage IIIC Lung Cancer AJCC v8, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8

Intervention / Treatment
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* Drug: Fluorine F 18 Ara-G


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: This study is open to all adult subjects with histological confirmation of NSCLC planned to undergo treatment with a PD-1 or PD-L1 inhibitor either as monotherapy or as combination therapy with concurrent chemotherapy as treatment for advanced/metastatic disease Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 or 3 at the time of enrollment Patient with life expectancy >= 24 weeks from the time of screening to the study Ability to sign and understand the Institutional Review Board (IRB)-approved consent form in English Ability to remain motionless for up to 30 minutes per scan Exclusion Criteria: Patients with severe claustrophobia (patients with milder forms of claustrophobia that can be successfully allayed with oral anxiolytic therapy are allowed) Severe impaired renal function with estimated glomerular filtration rate < 30 mL/min/1.73 m^2 and/or on dialysis Pregnancy Breast feeding an infant Prior treatment with anti-PD-1/PD-L1 inhibitor Localized/locally advanced disease with anti PD-1/PD-L1 given as consolidation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic ([18F]-AraG)<br>Patients receive [18F]-AraG IV and then undergo PET/CT over 2 hours at baseline and within 2 weeks after starting immunotherapy. Patients may also undergo blood sample collection. | Drug: Fluorine F 18 Ara-G<br>* Given IV<br>* Other names: [18F]F-AraG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluorine F 18 Ara-G ([18F]-AraG) uptake values in advanced non-small cell lung cancer (NSCLC) before and after treatment with anti-PD-1/PD-L1 therapy obtained | The positron emission tomography (PET) images will be interpreted qualitatively and semi-quantitatively on a lesion-by-lesion basis. Semi-quantitative analysis will be employed as follows: (a) Regions of interest (ROIs) will be placed around tracer avid foci suspicious for malignancy in order to obtain standardized uptake value (SUV) parameters, including maximum SUV (SUVmax), SUVpeak, SUVmean; (b) SUV data will be recorded along with volumetric and positional information in a standardized form. | Baseline up to within 2 weeks after starting immunotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in SUV | All SUV measurements will be summarized descriptively, separately for baseline and follow-up. Descriptive statistics for the SUVs will be done on a subject basis and a per lesion basis. Graphical summaries including box plots will be prepared to illustrate distributions and detect outliers or other findings; numerical summaries will include, mean, standard deviation (SD), median, and range as appropriate. For each target lesion, the scan 1 and scan 2 SUV will be determined and compared. A mixed-model repeated-measures analysis of variance (ANOVA) will be used to estimate the mean change in SUV from scan 1 to scan 2, allowing for possible need to account for between-patient random variation both in baseline level of SUV and amount of change. The primary result will be an estimate of the mean change in SUV, with a 95% confidence interval, along with the between patient and within-patient, between-lesion variation. | Baseline up to within 2 weeks after starting immunotherapy | 
| Correlation between [18F]-AraG uptake and clinical response |  | Baseline up to within 2 weeks after starting immunotherapy |