Early Response Evaluation in NSCLC Patients Treated With Immunotherapy

Study Overview
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Brief Summary
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A pilot study with biomarker exploration.50 patients with stage IV non-small cell lung cancer (NSCLC) that are eligible for treatment with nivolumab. Patients will undergo a 18F-FDG-PET/CT and EBUS-FNA of the lymph nodes and have blood drawn before and after immune checkpoint inhibitor treatment to compare tumor FDG uptake and to identify changes in the immune effector cell subsets in TDLNs. Blood will be drawn in parallel to compare the distribution of immune effector cell subsets before and after treatment initiation. Because of the possible burden for patients, the EBUS-FNA is not mandatory to complete the study and is there for an exploratory objective. Also blood will be drawn for a tumor mutational burden at baseline. The first six patients will undergo a dynamic PET-CT scan in addition to a static scan to study the influence of possible immunotherapy induced changes to the body distribution and kinetics of FDG..

Detailed Description
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Early response evaluation with 18F-FDG PET/CT and immunological profiling of circulating immune cells and tumor-draining lymph nodes in non-small cell lung cancer patients treated with immunotherapy.

Official Title
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Early Response Evaluation With 18F-FDG PET/CT and Immunological Profiling of Circulating Immune Cells and Tumor-draining Lymph Nodes in Non-small Cell Lung Cancer Patients Treated With Immunotherapy.

Conditions
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NSCLC, Stage IV

Intervention / Treatment
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* Diagnostic Test: 18F-FDG PET-CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: willing and able to provide written informed consent for the study. ≥ 18 years of age on day of signing informed consent. confirmed diagnosis of NSCLC. Histological tumor biopsy for PD-L1 IHC assessment (DAKO assay) available. Ipsilateral hilar or mediastinal lymph node with a short axis diameter ≥1 cm. Eligible and planned to receive nivolumab according to EMA label and national guidelines. Measurable disease according to RECIST v1.1. WHO performance status of 0-2. Exclusion Criteria: Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to baseline PET-scan. Has an active infection or had an active infection within 2 weeks prior to baseline PET-scan. Has a known history of hypersensitivity to contrast material. Isolated distant relapse after curative intent treatment for stage I-III NSCLC.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Nivolumab<br>Nivolumab treatment according to label: 3 mg/kg nivolumab IV Q2W, 240mg Q2W or 480mg Q4W as an IV infusion until disease progression or unacceptable toxicity. FDG PET-CT will be performed at baseline and between 7 and 14 days after treatment initiation | Diagnostic Test: 18F-FDG PET-CT<br>* 18F-FDG PET-CT scan<br>* Other names: Tracer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of collected immune cells by FNA EBUS will be assesed using flow cytometry. | The change in the percentages of selected immune cell parameters (CD4+ T, CD8+ T cells) after immunotherapy treatment as compared to baseline will be calculated | Baseline and at the end of cycle 1 (each cycle is 14 days). | 
| Percentage of collected immune cells by FNA EBUS will be assesed using flow cytometry. | The change in the percentages of selected immune cell parameters (CD8+ T cells) after immunotherapy treatment as compared to baseline will be calculated | Baseline and at the end of cycle 1 (each cycle is 14 days). | 
| FDG PET-CT analysis | Parameter change (SUVpeak) between both scans will be measured. | Baseline and at the end of cycle 1 (each cycle is 14 days). | 
| FDG PET-CT analysis | Parameter change (SUVmax) between both scans will be measured. | Baseline and at the end of cycle 1 (each cycle is 14 days). | 
| FDG PET-CT analysis | Parameter change (SUVmean) between both scans will be measured. | Baseline and at the end of cycle 1 (each cycle is 14 days). | 
| Peripheral blood mononuclear cells will be isolated and counted using FACS | PBMC's will be counted at two timepoints. Change between both timepoints will be assessed. | Baseline and at the end of cycle 1 (each cycle is 14 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-L1 expression, eligible for treatment with nivolumab