\[18F\]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).
Histologically confirmed NSCLC, a histological biopsy is mandatory, negative for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations
Be willing to provide either archival biopsy or fresh biopsy at screening.
Stage IIIB-IV patients that are planned to be treated with anti-PD-1 monotherapy
High PD-L-1 expression (≥50% TPS)
Subjects 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.
Untreated or symptomatic brain metastases
Additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
Evidence of interstitial lung disease or active, non-infectious pneumonitis.
Single group
[18F]F-AraG PET scan
Diagnostic test\[18F\]F-AraG PET scans are performed to assess the accumulation of activated T-cells in the tumour and healthy tissue.
To 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.
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.
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.
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.
To assess the relationship between change of tumor uptake of [18F]F-AraG and changes in PBMC subsets
To correlate changes in tumor \[18F\]F-AraG uptake as measured between baseline and 2 weeks and 6 weeks on-treatment, with changes in the immune profile of peripheral blood mononuclear cells (PBMC) as measured between baseline and 2 weeks and 6 weeks on-treatment.
To visually correlate the [18F]F-AraG autoradiogram with immuno-histochemistry (IHC) read outs for tumor cells and T-cells
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Amsterdam UMC, location VUmc
Lead sponsor
Boehringer Ingelheim
Collaborator
