\[18F\]F-AraG is a promising tracer to image activated T-cells with positron emission tomography (PET). The aim of the SHARP trial is to investigate changes in \[18F\]F-AraG uptake following Anti-PD-1 therapy in patients with non-small cell lung cancer (NSCLC).
The efficacy of immunotherapy and patient selection for combinatorial immunotherapy strategies would greatly improve if the tumor microenvironment (TME) could be characterized more accurately. Positron emission tomography (PET) using tracers that target immune cell subsets may provide a non-invasive means to immune profile the TME. Imaging T-cells can help in identifying 'hot' tumors, or parts of the tumor mass that have high concentrations of tumor infiltrating T-cells and also provide information on its activation. A promising tracer to image activated T-cells is \[18F\]F-AraG. Based on the hypothesis that \[18F\]F-AraG will accumulate in activated T-cells, it is expected that \[18F\]F-AraG and PET will enable to identify tumors and tumor areas with high concentrations of tumor infiltrating activated T-cells on pathological assessment. In the SHARP trial, participants receive 3 longitudinal \[18F\]F-AraG PET scans during anti-PD-1 immunotherapy to explore the changes in uptake of \[18F\]F-AraG during the treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
15
\[18F\]F-AraG PET scans are performed to assess the accumulation of activated T-cells in the tumour and healthy tissue.
Amsterdam UMC, location VU University Medical Center
Amsterdam, Netherlands
RECRUITINGTo assess the relative change in uptake of [18F]F-AraG in tumor lesions and lymphoid organs on anti-PD-1 treatment
To assess the changes in tracer uptake in all tumor lesions and lymphoid organs (lymph nodes, spleen) between baseline and after 2 and 6 weeks on-treatment per \[18F\]F-AraG PET scan.
Time frame: six weeks
To correlate baseline [18F]F-AraG uptake and tumor response to anti-PD-1 therapy
To correlate baseline tumor \[18F\]F-AraG uptake and objective response rate (ORR, defined as complete response (CR) and partial response (PR)) at 6 and 12 weeks.
Time frame: twelve weeks
To correlate the change in [18F]F-AraG uptake between baseline and on-treatment and tumor response to anti-PD-1 therapy
To correlate change in tumor \[18F\]F-AraG uptake as measured between baseline and 2 weeks and 6 weeks on-treatment, respectively, and objective response rate (ORR, defined as complete response (CR) and partial response (PR)) at 6 and 12 weeks.
Time frame: twelve weeks
To assess the relationship between baseline tumor uptake of [18F]F-AraG, T cell infiltration and activation state at baseline
To correlate tumor \[18F\]F-AraG uptake at baseline with viable tumor cells and T-cell infiltration in tumor and stroma using multiplex IHC (VECTRA) analysis panels for T-cell subsets, for monocytes and metabolic milieu, and panels directed at resistance as well as RNA sequencing to assess tumor microenvironment.
Time frame: twelve weeks
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