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

Primary Purpose

Advanced Stage Non-small Cell Lung Cancer

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
[18F]F-AraG PET scan
Sponsored by
Amsterdam UMC, location VUmc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Advanced Stage Non-small Cell Lung Cancer focused on measuring Positron Emission Tomography, [18F]F-AraG, T-Lymphocytes, Longitudinal Imaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Amsterdam UMC, location VU University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

[18F]F-AraG PET procedures

Arm Description

All patients will undergo a total of 3 [18F]F-AraG PET scanning procedures at T=0, T=2 weeks and T=6 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
December 21, 2022
Last Updated
January 17, 2023
Sponsor
Amsterdam UMC, location VUmc
Collaborators
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT05701176
Brief Title
A Clinical Imaging Study of the Changes in [18F]F-AraG Uptake Following Anti-PD-1 Therapy in Non-small Cell Lung Cancer
Acronym
SHARP
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
Collaborators
Boehringer Ingelheim

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Stage Non-small Cell Lung Cancer
Keywords
Positron Emission Tomography, [18F]F-AraG, T-Lymphocytes, Longitudinal Imaging

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
[18F]F-AraG PET procedures
Arm Type
Experimental
Arm Description
All patients will undergo a total of 3 [18F]F-AraG PET scanning procedures at T=0, T=2 weeks and T=6 weeks.
Intervention Type
Diagnostic Test
Intervention Name(s)
[18F]F-AraG PET scan
Intervention Description
[18F]F-AraG PET scans are performed to assess the accumulation of activated T-cells in the tumour and healthy tissue.
Primary Outcome Measure Information:
Title
To assess the relative change in uptake of [18F]F-AraG in tumor lesions and lymphoid organs on anti-PD-1 treatment
Description
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
Title
To correlate baseline [18F]F-AraG uptake and tumor response to anti-PD-1 therapy
Description
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
Title
To correlate the change in [18F]F-AraG uptake between baseline and on-treatment and tumor response to anti-PD-1 therapy
Description
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
Secondary Outcome Measure Information:
Title
To assess the relationship between baseline tumor uptake of [18F]F-AraG, T cell infiltration and activation state at baseline
Description
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
Other Pre-specified Outcome Measures:
Title
To assess the relationship between change of tumor uptake of [18F]F-AraG and changes in PBMC subsets
Description
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.
Time Frame
six weeks
Title
To visually correlate the [18F]F-AraG autoradiogram with immuno-histochemistry (IHC) read outs for tumor cells and T-cells
Time Frame
twelve weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Idris Bahce, MD, PhD
Phone
+31204444782
Email
i.bahce@amsterdamumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Idris Bahce, MD, PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam UMC, location VU University Medical Center
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Idris Bahce, MD, PhD
Phone
+31204444782
Email
i.bahce@amsterdamumc.nl

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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