Clinical development updates with [68Ga]FAPI-46 and [18F]FAPI-74

Introduction: Fibroblast activation protein (FAP) is a type II transmembrane glycoprotein that has shown to be highly expressed in cancer associated fibroblasts (CAFs) in the tumor microenvironment of many malignancies. The FAPI (FAP inhibitor) family of compounds targeting FAP have demonstrated ideal biodistribution and specificity as radiolabeled products for PET imaging with over 4000 patients imaged to date with FAPI family of tracers.

Methods: [⁶⁸Ga]FAPI-46 as the lead gallium labelled and [¹⁸F]FAPI-74 with a longer half life as the lead flourine-18 labelled product possess excellent characteristics for PET imaging. These two products were developed in Professor Uwe Haberkorn’s lab at Heidelberg University and licensed by SOFIE Biosciences for diagnostic and companion diagnostic use. These products have entered Phase 2 clinical studies in the United States for diagnostic use in cancers of digestive tracts. Here we describe the latest clinical development updates for these products.

Results: [⁶⁸Ga]FAPI-46 is in a Phase 2 clinical trial study of patients with histopathologically proven resectable or borderline resectable Pancreatic Ductal Carcinoma (PDAC) (NCT05262855). The design of the study includes two cohorts of patients. In cohort 1 patients receive [⁶⁸Ga]FAPI-46 PET/CT followed by surgical resection with no treatment prior to surgery. In cohort 2 patients receive [⁶⁸Ga]FAPI-46 PET/CT before and after neoadjuvant therapy, followed by surgical resection. The key objective for the study is to evaluate the performance [sensitivity, specificity, accuracy] of [⁶⁸Ga]FAPI-46 PET imaging to detect tumor cells and FAP-expressing cells using histopathology and FAP immunohistochemistry respectively. Five trial sites have been identified for this study. NYU Langone and Mayo Clinic are the first two activated sites, followed by three additional sites in the process of activation. Sixty patients are included as part of the study, expected to be 50-75% completed by the end of 2023.

In Q1 of 2023, [¹⁸F]FAPI-74 will be entering Phase 2 clinical study in patients with Gastrointestinal Cancers, which include hepatocellular carcinoma, cholangiocarcinoma, gastric, pancreatic and colorectal cancer (NCT05641896). Each patient will receive one [¹⁸F]FAPI-74 PET scan along with a tissue sample taken in the form of biopsy and/or surgical resection, with no treatment provided between time of tissue obtained and [¹⁸F]FAPI-74 PET. The primary objective is to evaluate the positive predictive value of [¹⁸F]FAPI-74 PET images in detecting FAP-expressing cells using immunohistochemistry. Five clinical trial sites have been identified for this study with the first site planned for activation by March 2023. Approximately 120 patients are expected to be enrolled in the study with 50% study completion to be achieved by the end of 2023.

Both studies will also evaluate patient safety along with exploratory comparison to standard of care imaging.

Conclusions: [⁶⁸Ga]FAPI-46 and [¹⁸F]FAPI-74 are in Phase 2 clinical studies being evaluated in cancers of the digestive system. The studies evaluate the performance of FAPI PET in detecting disease state and FAP expressing cells. Both studies are expected to have 100% of the trial sites activated and reach minimum 50% completion status by the end of 2023.