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

University of Tennessee

Status and phase: Unknown; Phase 1

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: 18F-AraG

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04052412

4513

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 2 estimated patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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2 participants in 2 patient groups

NSCLC with Immunotherapy without radiation

Experimental group

Description:

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

Treatment:

Drug: 18F-AraG

NSCLC with Immunotherapy with radiation

Experimental group

Description:

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

Treatment:

Drug: 18F-AraG