Novartis has initiated a first-in-human Phase I trial of [⁶⁸Ga]Ga-DFC413 (JFI447), a Gallium-68-labeled radioligand designed to image fibroblast activation protein (FAP)-expressing lesions across multiple solid tumor types. The study is strategically significant because it positions DFC413 as a potential companion diagnostic within Novartis's expanding FAP-targeted radioligand therapy program, where the therapeutic counterpart [¹⁷⁷Lu]Lu-NNS309 is already in clinical development.
The open-label, multicenter Phase I study (NCT07630961) enrolls approximately 66 adults with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple negative breast cancer (TNBC), colorectal cancer (CRC), or soft tissue sarcoma. The trial is structured in two sequential parts. Part 1 characterizes [⁶⁸Ga]Ga-DFC413 as a standalone imaging agent, with primary endpoints measuring radiotracer uptake in tumors and organs via standardized uptake value (SUV) and SUV ratio (SUVr) metrics across a four-hour PET imaging window. Part 2 introduces a direct head-to-head comparison against [⁶⁸Ga]Ga-NNS309 (FFG233), an established FAP-targeting PET agent already evaluated in Novartis's theranostic program, with the primary endpoint assessing concordance between the two tracers in detecting FAP-positive lesions per disease group. The trial is currently recruiting at a Novartis investigative site in Tokyo, with primary completion anticipated in January 2028, according to the trial record.
FAP is a serine protease selectively overexpressed on cancer-associated fibroblasts in the tumor stroma of most epithelial malignancies, with minimal expression in normal adult tissue. This differential expression makes FAP an attractive target for tumor imaging, particularly in cancers such as PDAC and TNBC where the stroma is dense and conventional imaging may underestimate disease burden. [⁶⁸Ga]Ga-DFC413 belongs to the FAPI (FAP inhibitor) class of small-molecule radiotracers, which bind FAP and, when labeled with the positron-emitting isotope Gallium-68, enable non-invasive PET visualization of FAP-expressing lesions. The structural details and precise pharmacophore of DFC413 have not been disclosed in any public source; its FAP-targeting mechanism is inferred from the trial record's explicit reference to FAP-positive lesion detection as a study endpoint.
The comparator agent, [⁶⁸Ga]Ga-NNS309, is part of a FAP-targeting library that Novartis licensed in March 2021 from iTheranostics, Inc., an affiliate of SOFIE Biosciences, which had itself licensed the compound class from the University of Heidelberg — the academic institution where the FAPI series originated. NNS309 is paired with a lutetium-177-labeled therapeutic counterpart, [¹⁷⁷Lu]Lu-NNS309, currently being evaluated in a separate Novartis Phase I study.