[18F]-AraG for the Detection of T-Cell Activation in Advanced Non-small Cell Lung Cancer Patients Undergoing PD-1/PD-L1-Directed Therapy

Early Phase 1

Withdrawn

• Conditions: Stage IIIA Lung Cancer AJCC v8; Stage IV Lung Cancer AJCC v8; Stage IIIB Lung Cancer AJCC v8; Advanced Lung Non-Small Cell Carcinoma; Metastatic Lung Non-Small Cell Carcinoma; Stage III Lung Cancer AJCC v8; Stage IIIC Lung Cancer AJCC v8; Stage IVA Lung Cancer AJCC v8; Stage IVB Lung Cancer AJCC v8
• Interventions: Drug: Fluorine F 18 Ara-G

• Registration Number: NCT04186988
• Lead Sponsor: University of California, Davis

Brief Summary

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 body (advanced), who are undergoing PD-1/PD-L1-directed therapy. \[18F\]-AraG is a "radiotracer" which attaches to immune cells directed at the cancer and shines a light that can be seen using a special camera, called a "positron emission tomography" or "PET" scanner. \[18F\]-AraG may improve the ability to detect a response of the cancer in the body to immunotherapy.

Detailed Description

PRIMARY OBJECTIVES:

I. To quantify fluorine F 18 Ara-G (\[18F\]-AraG) uptake (standardized uptake value \[SUV\]) in advanced non-small cell lung cancer (NSCLC) tumor (primary, nodal, and metastatic sites) at baseline and after 1 dose of anti-PD-1/PD-L1 therapy in both patients treated with PD-1/PD-L1 monotherapy and in patients treated with immunotherapy/chemotherapy combination therapy.

II. To correlate change in \[18F\]-AraG uptake before and after the start of therapy with radiographic response in patients treated with immunotherapy.

OUTLINE:

Patients receive \[18F\]-AraG intravenously (IV) and then undergo PET/CT over 2 hours at baseline and within 2 weeks after starting immunotherapy. Patients may also undergo blood sample collection.

After completion of study treatment, patients are followed for up to 12 months.

Study Timeline

• Study Start: 2019-11-05
• Study First Submitted: 2019-12-02
• Study First Submitted QC: 2019-12-02
• Study First Posted: 2019-12-05
• Primary Completion: 2020-03-12
• Study Completion: 2020-03-12
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-24
• Last Update Posted: 2022-02-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• This study is open to all adult subjects with histological confirmation of NSCLC planned to undergo treatment with a PD-1 or PD-L1 inhibitor either as monotherapy or as combination therapy with concurrent chemotherapy as treatment for advanced/metastatic disease
• Eastern Cooperative Oncology Group (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 sign and understand the Institutional Review Board (IRB)-approved consent form in English
• Ability to remain motionless for up to 30 minutes per scan

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 m^2 and/or on dialysis
• Pregnancy
• Breast feeding an infant
• Prior treatment with anti-PD-1/PD-L1 inhibitor
• Localized/locally advanced disease with anti PD-1/PD-L1 given as consolidation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic ([18F]-AraG)	Fluorine F 18 Ara-G	Patients receive \[18F\]-AraG IV and then undergo PET/CT over 2 hours at baseline and within 2 weeks after starting immunotherapy. Patients may also undergo blood sample collection.

Primary Outcome Measures

Name	Time	Method
Fluorine F 18 Ara-G ([18F]-AraG) uptake values in advanced non-small cell lung cancer (NSCLC) before and after treatment with anti-PD-1/PD-L1 therapy obtained	Baseline up to within 2 weeks after starting immunotherapy	The positron emission tomography (PET) images will be interpreted qualitatively and semi-quantitatively on a lesion-by-lesion basis. Semi-quantitative analysis will be employed as follows: (a) Regions of interest (ROIs) will be placed around tracer avid foci suspicious for malignancy in order to obtain standardized uptake value (SUV) parameters, including maximum SUV (SUVmax), SUVpeak, SUVmean; (b) SUV data will be recorded along with volumetric and positional information in a standardized form.

Secondary Outcome Measures

Name	Time	Method
Mean change in SUV	Baseline up to within 2 weeks after starting immunotherapy	All SUV measurements will be summarized descriptively, separately for baseline and follow-up. Descriptive statistics for the SUVs will be done on a subject basis and a per lesion basis. Graphical summaries including box plots will be prepared to illustrate distributions and detect outliers or other findings; numerical summaries will include, mean, standard deviation (SD), median, and range as appropriate. For each target lesion, the scan 1 and scan 2 SUV will be determined and compared. A mixed-model repeated-measures analysis of variance (ANOVA) will be used to estimate the mean change in SUV from scan 1 to scan 2, allowing for possible need to account for between-patient random variation both in baseline level of SUV and amount of change. The primary result will be an estimate of the mean change in SUV, with a 95% confidence interval, along with the between patient and within-patient, between-lesion variation.
Correlation between [18F]-AraG uptake and clinical response	Baseline up to within 2 weeks after starting immunotherapy