The iRelate is a PET imaging trial to compare two upcoming and promising T cell PET tracers. Following chemo-immuno therapy, as part of standard care, NSCLC patients will be recruited to receive two PET scans, shortly before their surgery. Both PET scans will be compared to each other, as well as compared to the pathological analysis of the resected tumor.
This study will provide detailed information on the unique as well as additive capacities of imaging biomarkers derived from the immune cell targeting PET tracers.
Histologically confirmed NSCLC
T1-4N0-2, lesion size of ≥2cm, at time of the restaging FDG PET/CT
Planned to undergo resection after chemo-IO according to routine treatment guidelines
Willing and able to provide written informed consent for the trial
Patients deemed inoperable
Patients who have received a splenectomy
Patients who have received any vaccination within 14 days of enrollment
Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day 0. Inhaled or topical steroids, and adrenal replacement steroid >10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Single group
[18F]F-AraG PET imaging
DrugPatients will receive a static whole-body PET scan following a \[18F\]F-AraG injection.
[89Zr]Zr-Df-Crefmirlimab PET imaging
DrugPatients will receive a static whole-body PET scan following a \[89Zr\]Zr-Df-Crefmirlimab injection.
To measure the spatial correlation of PET uptake of [18F]F-AraG and [89Zr]Zr-Df-Crefmirlimab in tumors and T-cell rich organs such as lymph nodes prior to resection.
The spatial overlap of the regions of uptake for both PET tracers will be assessed using the Dice Similarity Coefficient (DSC) as an established method
To measure the strength of correlation between the presence of CD8+ cells and T cell activation features in the resected tumor and lymph nodes with preoperative uptake of [89Zr]Zr-Df-Crefmirlimab and [18F]F-AraG, respectively.
The Pearson correlation coefficient between each tracer tumor uptake and the T cell features in regions of concordance and discordance.
To measure the strength of correlation of pathological response (i.e., the residual viable tumor cells percentage) in the resected tumor with preoperative uptake of [89Zr]Zr-Df-Crefmirlimab and [18F]F-AraG.
The Pearson correlation coefficient between each tracer tumor uptake and percentage of residual viable tumor cells (VTC) in regions of concordance and discordance and the maximal VTC of the entire tumor. The Pearson correlation coefficient between each tracer uptake and the T cell presence in resected lymph nodes (if present).
To explore the association of PET uptake of both tracers in tumor and T-cell rich organs such as lymph nodes with: The immune profile of the TME and resected lymph nodes beyond T cells. The immune profile of peripheral blood mononuclear cells (PBMCs)
The Pearson correlation coefficient between PET uptake and immune profile of the TME for tumor and T-cell rich organs. The Pearson correlation coefficient between PET uptake and immune profile of PBMCs for tumor + T-cell rich organs.
To quantify inter- and intra-tumoral heterogeneity of PET tracer uptake.
Voxel intensities for \[18F\]F-AraG and \[89Zr\]Zr-Df-Crefmirlimab PET images will be plotted against each other by means of scatter plots and joint histograms/kernel density plots to illustrate the degree of agreement in spatial distribution of both tracers with the VOIs.
To assess the relationship of metabolically active areas as assessed by [18F]F-FDG PET with areas of uptake derived from [18F]F-AraG and [89Zr]Zr-Df-Crefmirlimab PET.
The spatial overlap of the regions of uptake for the FDG, \[18F\]F-AraG and \[89Zr\]Zr-Df-Crefmirlimab PET tracers will be assessed using the Dice Similarity Coefficient (DSC) method.
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Amsterdam UMC, location VUmc
Lead sponsor
Foundation for the National Institutes of Health
Collaborator
