Clinical trial NCT05701176: A Clinical Imaging Study of the Changes in [18F]F-AraG Uptake Following Anti-PD-1 Therapy in Non-small Cell Lung Cancer
Official title: A Clinical Imaging Study of the Changes in [18F]F-AraG Uptake Following Anti-PD-1 Therapy in Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Advanced Stage Non-small Cell Lung Cancer
Keywords: Positron Emission Tomography
[18F]F-AraG
T-Lymphocytes
Longitudinal Imaging
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2023-01-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: \[18F\]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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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)
* No prior systemic therapy for the treatment of cancer
* Be willing and able to provide written informed consent for the trial.
* Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Be above 18 years of age on day of signing informed consent.

Exclusion Criteria:

* 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.
* Active infection requiring systemic therapy.
* A history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
* Active Hepatitis B or C.
* Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Patient is pregnant or breastfeeding or expecting to conceive within the projected duration of the trial, starting with the screening visit through 12 weeks after the last administration of \[18F\]F-AraG.

Primary outcomes:
measure: To assess the relative change in uptake of [18F]F-AraG in tumor lesions and lymphoid organs on anti-PD-1 treatment
timeFrame: six weeks
measure: To correlate baseline [18F]F-AraG uptake and tumor response to anti-PD-1 therapy
timeFrame: twelve weeks
measure: To correlate the change in [18F]F-AraG uptake between baseline and on-treatment and tumor response to anti-PD-1 therapy
timeFrame: twelve weeks
Secondary outcomes:
measure: To assess the relationship between baseline tumor uptake of [18F]F-AraG, T cell infiltration and activation state at baseline
timeFrame: twelve weeks
Other outcomes:
measure: To assess the relationship between change of tumor uptake of [18F]F-AraG and changes in PBMC subsets
timeFrame: six weeks
measure: To visually correlate the [18F]F-AraG autoradiogram with immuno-histochemistry (IHC) read outs for tumor cells and T-cells
timeFrame: twelve weeks
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VU University Medical Center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Idris Bahce, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: