Imaging for Lung Cancer

Overseen By Amy Mundisev

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CellSight Technologies, Inc.

Must be taking: Checkpoint inhibitors

Disqualifiers: Pregnancy, Nursing, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special type of imaging to evaluate the immune system's response to certain treatments for advanced non-small cell lung cancer (NSCLC). By using an advanced PET scan with [18F]F-AraG (also known as VisAcT or 2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine), the researchers aim to measure changes in the immune response before and during therapy. It targets patients with NSCLC undergoing specific immune-based treatments and can be followed at the University of Iowa. This research seeks to determine if these scans can predict treatment effectiveness. As a Phase 2 trial, it focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that [18F]F-AraG PET imaging is safe for evaluating immunological response in NSCLC patients?

Research has shown that [18F]F-AraG, used in PET scans to observe immune responses in cancer patients, has been studied for effectiveness and safety. One study found that [18F]F-AraG can help identify active T-cells, which play a crucial role in fighting cancer. This suggests the imaging agent is useful, and the study did not report any serious side effects from its use.

Another study examined how [18F]F-AraG moves through the body and found that it behaves as expected, without causing significant issues. These findings suggest that [18F]F-AraG is generally well-tolerated by patients and hasn't caused major problems in trials so far. However, since these are early results, more research is needed to confirm its safety in a larger number of patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]F-AraG because it offers a new approach to imaging for lung cancer, specifically in patients with advanced non-small cell lung cancer (NSCLC) undergoing PD-1/PD-L1 directed therapy. Unlike traditional imaging methods, [18F]F-AraG is unique in that it targets and binds to activated immune cells, providing a more detailed picture of how the body's immune system is responding to cancer therapy. This could potentially help doctors tailor treatments more precisely to each patient's needs. This innovative technique enhances our understanding of treatment efficacy in real-time, which is a significant step forward compared to conventional imaging methods that focus only on tumor size and structure.

What evidence suggests that this imaging technique is effective for evaluating immunological response in advanced NSCLC?

Research has shown that a special type of scan called [18F]F-AraG PET can track T-cell activity, which is part of the immune system, in patients with advanced non-small cell lung cancer (NSCLC). In this trial, participants receiving PD-1/PD-L1 directed therapy will undergo evaluation using this scan. Studies have found that [18F]F-AraG PET can detect immune system changes when patients receive checkpoint inhibitors, a type of cancer therapy. By observing these changes, [18F]F-AraG can help predict a patient's response to the treatment. This technique uses the body's immune activity as a marker to provide insights into treatment effectiveness over time. Early results suggest it can assist doctors in making better decisions about a patient's treatment plan. ^{1 3 6 7 8}

Who Is on the Research Team?

Muhammad Furqan

Principal Investigator

Holden Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who are about to start immunotherapy. They should be able to perform daily activities with ease or with some limitations (ECOG status 0, 1, or 2). Participants must also agree to follow-up visits at the University of Iowa.

Inclusion Criteria

Participants consent to be monitored at the University of Iowa.

I can take care of myself and perform daily activities.

My cancer can be measured by tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Imaging

Participants undergo pre-treatment [18F]F AraG PET/CT scans to evaluate baseline T-cell activation

1 week

1 visit (in-person)

Treatment

Participants receive PD-1/PD-L1 directed therapy and undergo on-treatment [18F]F AraG PET/CT scans

12 months

Multiple visits (in-person) for therapy and imaging

Follow-up

Participants are monitored for radiographic and clinical outcomes after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• [18F]F-AraG

Trial Overview [18F]F-AraG PET imaging is being tested in this study to see how well it shows the body's immune response to checkpoint inhibitor therapy in NSCLC patients. The trial involves scans before and during treatment, followed by a year-long observation period.

How Is the Trial Designed?

Group I: Advanced non small cell lung cancer (NSCLC) patients undergoing PD-1/PD-L1 directed therapy Experimental Treatment 1 Intervention

[18F]F-AraG is already approved in United States for the following indications:

Approved in United States as Nelarabine (prodrug of AraG) for:

• T-cell acute lymphoblastic leukemia
• T-cell lymphoblastic lymphoma

Who Is Running the Clinical Trial?

CellSight Technologies, Inc.

Lead Sponsor

Trials

18

Recruited

320+

Published Research Related to This Trial

The study successfully synthesized the first 18F-labelled ATM inhibitor, which allows for non-invasive imaging of ATM protein and tracking of the drug's pharmacokinetics, potentially aiding in personalized cancer treatment.

In vitro and in vivo evaluations showed that while the uptake of the 18F-labelled inhibitor was specific to ATM and could be blocked by known ATM inhibitors, its retention in cells decreased over time, indicating some limitations in its effectiveness for imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent. Fraser, CR., Ajenjo, J., Veal, M., et al.[2023]

The use of [18F]FDG-PET/CT is crucial for diagnosing and staging lung cancer, but its limitations have prompted the development of new PET tracers that target specific tumor characteristics.

While no new tracers have yet proven to replace [18F]FDG-PET/CT, they may enhance imaging by providing additional insights into tumor biology and heterogeneity, indicating a promising direction for future lung cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PET Tracers: Current Knowledge and Perspectives in Lung Cancer. Krarup, MMK., Fischer, BM., Christensen, TN.[2022]

FDG-PET imaging has significantly improved the assessment and staging of non-small cell lung cancer (NSCLC), leading to a reduction in unnecessary surgeries, as demonstrated by a randomized trial.

The technique not only aids in initial staging but also has prognostic value for evaluating treatment responses and detecting relapses, with ongoing developments in new molecular tracers promising even greater specificity for monitoring cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography in the management of non-small cell lung cancer. Vansteenkiste, JF., Stroobants, SG.[2019]

The study evaluated two thymidine analogs, FAU and FMAU, as potential PET imaging agents in SCID mice with human T-cell leukemia, showing that FMAU accumulates significantly in tumor tissue and incorporates into tumor DNA more effectively than FAU or thymidine.

FMAU demonstrated a higher concentration in tumor DNA, being 45% greater than thymidine and threefold greater than FAU, suggesting its potential as a functional PET imaging agent for tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice. Wang, H., Oliver, P., Nan, L., et al.[2020]

The novel imaging agent [(18)F]F-AraG was successfully synthesized with a radiochemical yield of 7-10%, demonstrating potential for use in positron emission tomography (PET) imaging of T cells.

Preliminary studies indicate that both leukemia cell lines and activated primary thymocytes effectively take up [(18)F]F-AraG, supporting its future application in imaging T-cell activity in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. Namavari, M., Chang, YF., Kusler, B., et al.[2021]

The study involving six healthy volunteers demonstrated that the radiolabeled nucleoside analog [18F]F-AraG is well tolerated, with no adverse effects reported after administration, indicating its safety for use in imaging.

Biodistribution results showed that [18F]F-AraG primarily accumulates in the kidneys and liver, aligning with its mechanism of action related to mitochondrial metabolism, making it a promising tracer for various applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. Levi, J., Duan, H., Yaghoubi, S., et al.[2022]

The new tracer 18F-fluoroaminosuberic acid (18F-FASu) shows higher early uptake in tumors compared to the conventional tracer 18F-fluorodeoxyglucose (18F-FDG), indicating its potential for better tumor assessment in PET imaging.

The influx rate of 18F-FASu is significantly correlated with the expression of the cystine/glutamate antiporter (xCT), suggesting that 18F-FASu uptake may be influenced by the tumor's oxidative stress levels, which could enhance its utility in evaluating tumor biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influx rate of 18F-fluoroaminosuberic acid reflects cystine/glutamate antiporter expression in tumour xenografts. Pitman, KE., Alluri, SR., Kristian, A., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04726215

NCT04726215 | Imaging of T-cell Activation With [18F]F- ... Imaging of T-cell Activation With [18F]F-AraG in Advanced Non Small Cell Lung Cancer. ClinicalTrials.gov ID NCT04726215. Sponsor CellSight Technologies, Inc ...

2. sutterhealth.org sutterhealth.org/research/clinical-trials/imaging-of-t-cell-activation-with-18ff-arag-in-advanced-ns-1049141788

Imaging of T-cell Activation With [18F]F-AraG in Advanced NS The main objectives of the study are to quantify the change in [18F]F AraG PET signal before and after CkIT therapy, and to correlate this change in [18F]F ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10543042/

Total-body Dynamic Imaging and Kinetic Modeling of 18F ... This study is the first report on dynamic imaging and kinetic modeling of 18F-AraG, as well as the first in-human report on using 18F-AraG in a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04186988?term=AREA%5BInterventionSearch%5D(%229-arabinofuranosylguanine%22)&rank=1

[18F]-AraG for the Detection of T-Cell Activation in ... This trial studies how well [18F]-AraG works in detecting T-cell activation in patients with non-small cell lung cancer that has spread to other places in the ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/early/2024/08/01/jnumed.123.267003

Total-Body Dynamic Imaging and Kinetic Modeling of [18F] ... The aim of this study was to obtain preliminary data on total-body pharmacokinetics of [18F]F-AraG as a potential quantitative biomarker for ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37790461/

Total-body Dynamic Imaging and Kinetic Modeling of 18 F ... The aim of this study was to obtain preliminary data on total-body pharmacokinetics of 18F-AraG, as a potential quantitative biomarker for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372257/

Total-Body Dynamic Imaging and Kinetic Modeling of [18F] ... This study introduces [ 18 F]F-AraG dynamic imaging and kinetic modeling as a noninvasive quantitative biomarker for evaluating the immune response to ...

8. ctv.veeva.com ctv.veeva.com/study/pet-imaging-with-18f-f-arag-in-advanced-non-small-cell-lung-cancer-nsclc

PET Imaging With [18F]F-AraG in Advanced Non-small Cell ... The purpose of this study is to find out how the radiotracer called [18F]F-AraG can help investigate changes in cancer's anti-tumor immune ...