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

Overview

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Care Provider)
  • Study Primary Completion Date: December 31, 2023

Detailed 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.

Interventions

  • Drug: 18F-AraG
    • 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.

Arms, Groups and Cohorts

  • Experimental: NSCLC with Immunotherapy without radiation
    • 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
  • Experimental: NSCLC with Immunotherapy with radiation
    • 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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • Assessment of biodistribution and kinetics differences between study arms
    • Time Frame: 6 months
    • Assessment of biodistribution and kinetics differences using activity concentration changes between patients undergoing immunotherapy with radiation and immunotherapy without radiation

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Tennessee
  • Collaborator
    • CellSight Technologies, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Dustin Osborne, PhD, Principal Investigator, University of Tennessee
  • Overall Contact(s)
    • Dustin R Osborne, PHD, 8653058264, DOSBORNE@UTMCK.EDU

References

Levi J, Lam T, Goth SR, Yaghoubi S, Bates J, Ren G, Jivan S, Huynh TL, Blecha JE, Khattri R, Schmidt KF, Jennings D, VanBrocklin H. Imaging of Activated T Cells as an Early Predictor of Immune Response to Anti-PD-1 Therapy. Cancer Res. 2019 Jul 1;79(13):3455-3465. doi: 10.1158/0008-5472.CAN-19-0267. Epub 2019 May 7.

Franc BL, Goth S, MacKenzie J, Li X, Blecha J, Lam T, Jivan S, Hawkins RA, VanBrocklin H. In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis. Mol Imaging. 2017 Jan 1;16:1536012117712638. doi: 10.1177/1536012117712638.

Ronald JA, Kim BS, Gowrishankar G, Namavari M, Alam IS, D'Souza A, Nishikii H, Chuang HY, Ilovich O, Lin CF, Reeves R, Shuhendler A, Hoehne A, Chan CT, Baker J, Yaghoubi SS, VanBrocklin HF, Hawkins R, Franc BL, Jivan S, Slater JB, Verdin EF, Gao KT, Benjamin J, Negrin R, Gambhir SS. A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Cancer Res. 2017 Jun 1;77(11):2893-2902. doi: 10.1158/0008-5472.CAN-16-2953.

Namavari M, Chang YF, Kusler B, Yaghoubi S, Mitchell BS, Gambhir SS. Synthesis of 2'-deoxy-2'-[18F]fluoro-9-beta-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. Mol Imaging Biol. 2011 Oct;13(5):812-8. doi: 10.1007/s11307-010-0414-x.

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