Imaging Advanced NSCLC Patients Undergoing PD-1/PD-L1 Directed Therapy Using [18F]-FARAG

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

This pilot study uses [18F]F AraG PET imaging to evaluate the immunological response to checkpoint inhibitor therapy (CkIT) in patients with advanced NSCLC tumors. The study's main objectives are to quantify the change in [18F]F AraG PET signal before and while on CkIT therapy and to correlate this change in [18F]F AraG PET signal with radiographic response.

To explore these objectives, eligible subjects will undergo pre- and on - CkIT treatment [18F]F AraG PET/CT scans, and will be followed up for 12 months for assessment of radiographic and clinical outcomes. This study is a single-site, open label, non randomized, single arm pilot trial. Patients and care providers will not be blinded to any part of the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: [18F]F-AraG

Detailed Description

Checkpoint inhibitor therapy has led to impressive clinical successes, providing objective and durable responses in patients with advanced cancers that previously had few treatment options. Unfortunately, immunotherapy works only in a relatively small fraction of patients with solid tumors.

The current standard of care anatomic imaging adequately assessed treatment efficacy in the pre-immunotherapy era, when tumor volume burden directly correlated with clinical outcomes. However, anatomic imaging is found to be limited due to the cellular and molecular nature of early responses to immunotherapy. PET imaging is a sensitive technique that uses radiolabeled agents to visualize the distribution of specific molecular targets in the body. Based on its ability to pinpoint molecular activity, PET imaging agents that target key players of the immune response could offer a powerful noninvasive tool for evaluating complex immunologic processes within the body.

[18F]F-AraG was developed as an agent for imaging activated T cells. [18F]F-AraG is an 18F-labeled analog of 9-b-D-Arabinofuranosylguanine a compound that has shown selective accumulation in T cells and whose prodrug, nelarabine, is FDA-approved for the treatment of patients with T cell acute lymphoblastic leukemia and T cell lymphoblastic lymphoma. [18F]F-AraG is independent of the type of immunotherapy regimen being administered adoptive cell therapy, checkpoint inhibitors, cancer vaccines or a combination of immunotherapy and conventional medicines. In vivo, real-time imaging of activated T cells in solid tumors before and at a timepoint during and after CkIT therapy can help understand the effects of checkpoint blockade therapy. Additionally, in vivo whole-body imaging of activated T cells can provide critical information about the effect of immunomodulation in resulting in autoimmunity, and thus help predict adverse events of immunotherapy.

To sum up, characterizing the immune system alterations in vivo, in real-time, and non-invasively using PET imaging may enable us to predict better which patients will benefit from which Checkpoint Inhibitor Therapy (CkIT) treatment regimen.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Mundisev; Phone Number: 319-356-1445; Email: amy-mundisev@uiowa.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed NSCLC and planned to undergo immunotherapy as monotherapy or as combination therapy for advanced/metastatic disease.
2. Measurable disease.
3. ECOG performance status of 0, 1 or 2.
4. Subjects are willing to be followed at the University of Iowa.

Exclusion Criteria:

1. Serious comorbidities that in the opinion of the investigator/sponsor could compromise protocol objectives.
2. Pregnant women or nursing mothers.
3. Patients with severe claustrophobia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Advanced non small cell lung cancer (NSCLC) patients undergoing PD-1/PD-L1 directed therapy	Drug: [18F]F-AraG; Two PET scans

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[18F]F-AraG Quantification	Quantitative assessment of tracer uptake by Standardized Uptake Value (SUV) based measurements within volumes of interest on pre- and on-treatment [18F]F AraG PET scans compared.	One Year
[18F]F AraG Correlation	Comparison of quantitative change in tracer uptake between pre- and on-treatment with radiographic outcomes as defined as Complete Response (CR) + Partial Response (PR) + stable disease (SD) > 4 months.	One Year

Collaborators and Investigators

• Sponsor: CellSight Technologies, Inc.
• Investigators: Principal Investigator: Muhammad Furqan, M.D., Holden Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

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: CST-FARAG-IO-UIOW-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No