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

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

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.

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.

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.