Biodistribution and Kinetics of 18F-AraG in Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study is to assess the biodistribution and kinetics of a novel T-cell imaging agent in non-small cell lung cancer patients undergoing immunotherapy with and without adjuvant radiation therapy. This study is assessing the change in kinetics that occurs in this patient population to better understand the distribution of this compound in patient disease circumstances.

Detailed Description
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The overall goal of this project is to evaluate the ability of [18F]-AraG, a novel T-cell activation imaging biomarker, to measure T-cell activation before and after treatment with programmed death (PD) PD-1/PD-L1 inhibition and with PD-1/PD-L1 inhibition plus radiation therapy in NSCLC patients. Early preclinical and clinical studies have shown promise for immunotherapy treatments for several malignancies [1]. Immunotherapy is expected to grow in importance; however, it presents difficult challenges for response assessment. For instance, successfully treated tumors may actually increase in size after therapy due to inflammation and only later shrink [2]. RECIST criteria [3] designed to detect early effects of cytotoxic agents by size reduction, or the more recently proposed immune-related response criteria (irRC) [4] do not allow an early assessment of immunotherapeutic response since both depend on tumor size change. Furthermore, FDG PET is confounded by inflammatory effects causing hypermetabolism [5] [6]. Thus, it is imperative to develop new imaging and analysis protocols to evaluate immune-checkpoint blockade approaches. A method that evaluates T cell activation would permit an assessment of a basic first step in the process of assessing immunotherapy efficacy. There are two main goals associated with this project. We propose to 1) assess the [18F]-AraG biodistribution and kinetics, in non-small cell lung cancer (NSCLC) tumor(s) and tumor draining lymph nodes on [18F]-AraG PET/CT imaging before and after 1 course of immunotherapy and 1 course of immunotherapy plus radiation 2) correlate (potential) change in [18F]-AraG uptake within the tumor(s) or tumor draining lymph nodes with clinical and pathologic response in patients treated with immunotherapy.

Official Title
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Biodistribution and Kinetics of 18F-AraG in Non-Small Cell Lung Cancer Patients Before and After Immunotherapy With and Without Radiation

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: 18F-AraG


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 enrolled in the parent protocol. Age 21 years of age or greater 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 give informed consent 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 m2 and/or on dialysis. Pregnancy Breast Feeding an infant Unable to tolerate the expected radiation therapy prescription

Ages Eligible for Study
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Minimum Age: 21 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a biodistribution and kinetics study looking at the uptake of 18F-AraG in non-small cell lung cancer patients in 3 different arms as follows: Non-small cell lung cancer undergoing immunotherapy without radiation therapy Non-small cell lung cancer undergoing immunotherapy with adjuvant radiation therapy
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NSCLC with Immunotherapy without radiation<br>The biodistribution and kinetics of the 18F-AraG compound will be assessed in non-small cell lung cancer patients undergoing immunotherapy without adjuvant radiation therapy | Drug: 18F-AraG<br>* All arms of the study will receive an injection of 18F-AraG while on the PET imaging system. Following a 6 minute scan over the heart to acquire input function data, the patient will undergo a 1 hour multi-pass whole-body dynamic PET/CT acquisition to gather whole-body biodistribution data.<br>|
| Experimental: NSCLC with Immunotherapy with radiation<br>The biodistribution and kinetics of the 18F-AraG compound will be assessed in non-small cell lung cancer patients undergoing immunotherapy with adjuvant radiation therapy | Drug: 18F-AraG<br>* All arms of the study will receive an injection of 18F-AraG while on the PET imaging system. Following a 6 minute scan over the heart to acquire input function data, the patient will undergo a 1 hour multi-pass whole-body dynamic PET/CT acquisition to gather whole-body biodistribution data.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution of 18F-AraG | Assessment of the distribution of 18F-AraG in patients with non-small cell lung cancer using activity concentration | Up to 90 minutes post injection of 18F-AraG | 
| Kinetics of 18F-AraG | Assessment of the rate of uptake using activity concentration of 18F-AraG in regions found to have significant AraG uptake | Up to 90 minutes post injection of 18F-AraG | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of biodistribution and kinetics differences between study arms | Assessment of biodistribution and kinetics differences using activity concentration changes between patients undergoing immunotherapy with radiation and immunotherapy without radiation | 6 months |