Molecular Imaging of FAP Expressing Cancer-associated Fibroblasts in NSCLC Treated With Immune-checkpoint Inhibitors

Study Overview
=================
Brief Summary
-----------------
Evaluation of the relation between baseline fibroblast activation protein (FAP) expression based on Ga-FAPI uptake with patient outcome among NSCLC patients receiving immunotherapy for recurrent/metastatic disease.

Detailed Description
-----------------
Fibroblast activation protein (FAP), a type II membrane glycoprotein, is selectively expressed by cancer-associated fibroblasts (CAFs) in more than 90% of epithelial carcinomas. FAP also regulates antitumor immune response. For these reasons, FAP is an attractive target and molecular imaging biomarker to assess CAFs and the tumour's landscape before and during immunotherapy. The PET radiotracer 68Ga-FAPI (Fibroblast activation protein inhibitor) allows the visualisation and quantification of CAFs.This study will use a non-invasive technique to assess CAFs before and during immunotherapy and to evaluate diverse predictive biomarkers in a prospective setting studying simultaneously CAFs (using 68Ga-FAPI) and cfDNA.

Official Title
-----------------
Molecular Imaging of FAP Expressing Cancer-associated Fibroblasts in NSCLC Treated With Immune-checkpoint Inhibitors

Conditions
-----------------
Non Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Procedure: FAPI PET/CT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age above 18 years. Pathologically- proven non-small-cell lung cancer (NSCLC). Proposed for treatment with anti-PD-(L)1 alone or in combination with chemotherapy and/or anti-CTLA4 in the advanced setting. ECOG Performance status ≤2. Patient's written informed consent obtained prior to any study procedure. Exclusion Criteria: Surgery and/or radiotherapy to thoracic region within the last 8 weeks or anti-cancer systemic therapy within the last 2 weeks. Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and c-ros oncogene (ROS1) mutations. Pregnant and lactating women Previous or concurrent malignancy diagnosed within the last 2 years except adequately treated in situ carcinoma of the cervix uteri, localised (T1N0) low grade (Gleason score 6) prostate cancer undergoing active surveillance and basal or squamous cell skin cancer. Subjects with another significant medical condition which, in the investigator's opinion, may interfere with the completion of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FAPI PET/CT<br>The radiopharmaceutical 68Gallium-FAPI-46 (FAPI) is injected intravenously for molecular imaging of FAP expression with FAPI PET/CT in patients with NSCLC with an indication for immunotherapy | Procedure: FAPI PET/CT<br>* The radiopharmaceutical 68Gallium-FAPI-46 (FAPI) is injected intravenously for molecular imaging of FAP expression with FAPI PET/CT.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Patient outcome assessed by progression-free survival (PFS) defined as the time from the start of immunotherapy until disease progression* or death by any cause during the period of active and routine follow-up (overall PFS) | From date of inclusion until the date of first documented progression (RECIST) or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Patient outcome assessed by 0verall survival (OS) defined as the time from the start of immunotherapy until death by any cause. | until death by any cause, assessed up to 24 months | 
| Objective response rate | Patient outcome assessed by objective response rate based on iRECIST criteria • Kinetics of imaging biomarkers assessed with 68Ga-FAPI PET/CT at baseline and during treatment - examples of kinetics of imaging biomarkers: ΔSUVmax / ΔSUVpeak / ΔUptake-Volume. | From date of inclusion until the date of first documented progression (RECIST) or date of death from any cause, whichever came first, assessed up to 24 months | 
| cfDNA | Kinetics of cfDNA values at baseline and during treatment | From date of inclusion until the date of last FAPI PET/CT (6 weeks after start immunotherapy) | 
| Number of lesions | Number of metastatic lesions and the imaging biomarkers (SUVmax / SUVpeak / Uptake-Volume / Tumour-to-Background ratio) of the lesions on 68Ga-FAPI PET/CT and 18F-FDG PET/CT | From date of inclusion until the date of first documented progression (RECIST) or date of death from any cause, whichever came first, assessed up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunotherapy, FAPI-46, Non Small Cell Lung Cancer, PET, PET/CT, fibroblast activation protein, fibroblast activation protein inhibitor