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

Overview

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.

Interventions

• Procedure FAPI PET/CT
  The radiopharmaceutical 68Gallium-FAPI-46 (FAPI) is injected intravenously for molecular imaging of FAP expression with FAPI PET/CT.

Primary outcome measures

• Progression free survival [Time frame: 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 (4)

• Overall survival [Time frame: until death by any cause, assessed up to 24 months]
• Objective response rate [Time frame: 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 [Time frame: From date of inclusion until the date of last FAPI PET/CT (6 weeks after start immunotherapy)]
• Number of lesions [Time frame: 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]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Belgium · 1 center

• Institut Jules Bordet — Brussels

Identifiers

NCT: NCT06107608 · IJB-MN-LIFE1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗