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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: 18F-AraG

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.

• Study Type: Interventional
• Enrollment (Anticipated): 2
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dustin R Osborne, PHD; Phone Number: 8653058264; Email: DOSBORNE@UTMCK.EDU
• Study Contact Backup: Name: Melissa Weaver; Phone Number: 8653056181; Email: mweaver@utmck.edu

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center
      • Contact: Shelley Acuff; Phone Number: 8653056312; Email: sacuff@utmck.edu
      • Contact: Melissa Weaver; Phone Number: 865-305-6181; Email: mweaver@utmck.edu
      • Principal Investigator: Dustin Osborne, PhD
      • Principal Investigator: Joseph Kelley, MD
      • Principal Investigator: Francis J Turner, MD
      • Sub-Investigator: Yitong Fu, MD
      • Sub-Investigator: Jacob Noe, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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.
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	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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Tennessee
• Collaborators: CellSight Technologies, Inc.
• Investigators: Principal Investigator: Dustin Osborne, PhD, University of Tennessee

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 23, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 13, 2022
• Last Update Submitted That Met QC Criteria: May 12, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 4513

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No