A Clinical Imaging Study of the Changes in [18F]F-AraG Uptake Following Anti-PD-1 Therapy in Non-small Cell Lung Cancer (SHARP)

[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).

Study Overview

• Status: Recruiting
• Conditions: Advanced Stage Non-small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: [18F]F-AraG PET scan

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.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Idris Bahce, MD, PhD; Phone Number: +31204444782; Email: i.bahce@amsterdamumc.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • Amsterdam UMC, location VU University Medical Center
    • Contact: Idris Bahce, MD, PhD; Phone Number: +31204444782; Email: i.bahce@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: [18F]F-AraG PET procedures; All patients will undergo a total of 3 [18F]F-AraG PET scanning procedures at T=0, T=2 weeks and T=6 weeks.	Diagnostic test: [18F]F-AraG PET scan; [18F]F-AraG PET scans are performed to assess the accumulation of activated T-cells in the tumour and healthy tissue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	twelve weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	twelve weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	six weeks
To visually correlate the [18F]F-AraG autoradiogram with immuno-histochemistry (IHC) read outs for tumor cells and T-cells		twelve weeks

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: Boehringer Ingelheim
• Investigators: Principal Investigator: Idris Bahce, MD, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2022
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 17, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Positron Emission Tomography; T-Lymphocytes; [18F]F-AraG; Longitudinal Imaging
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: NL78588.029.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No