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 trial's diagnostic purpose carries strategic weight: Novartis is building a FAP-targeted theranostic platform, and the imaging agent is intended to pair with a therapeutic lutetium-177 counterpart, [177Lu]Lu-DFC413, currently in separate development. Whether [68Ga]Ga-DFC413 can reliably identify FAP-positive tumors across histologically distinct cancers will determine its utility as a patient selection tool for that therapeutic program.
The open-label, multicenter Phase I study (NCT07630961) enrolls approximately 66 adults with locally advanced or metastatic pancreatic ductal adenocarcinoma, non-small cell lung cancer, HR+/HER2- breast cancer, triple negative breast cancer, colorectal cancer, or soft tissue sarcoma. The trial is structured in two sequential parts: Part 1 characterizes the biodistribution, PET uptake kinetics, dosimetry, and pharmacokinetics of [68Ga]Ga-DFC413 following a single administered dose; Part 2 compares [68Ga]Ga-DFC413 head-to-head with [68Ga]Ga-NNS309 (FFG233), Novartis's established FAP-imaging agent, with patients receiving both tracers in crossover sequence. Primary endpoints in Part 1 measure standardized uptake values (SUV and SUVr) in tumors and organs over a 240-minute window; Part 2's primary endpoint assesses concordance between the two agents in detecting target lesions across disease groups. The trial is recruiting at a Novartis investigative site in Tokyo, with primary completion anticipated in January 2028, according to the trial record.
FAP is a cell-surface serine protease expressed predominantly by cancer-associated fibroblasts within the tumor stroma of most epithelial solid tumors, with low expression in normal adult tissue. This stromal expression pattern makes FAP an attractive imaging target because it is not restricted to a single tumor histology, potentially enabling a single tracer to serve multiple indications. [68Ga]Ga-DFC413 binds FAP-expressing cells and, following gallium-68 chelation, generates a PET signal that can be quantified to assess lesion-level FAP expression. The chemical scaffold of DFC413 has not been disclosed in publicly available sources, and its origin — whether developed internally by Novartis or in-licensed — remains unconfirmed.
The comparator, [68Ga]Ga-NNS309, has a well-documented provenance. It is the imaging form of FAP-2286, a cyclic FAP-binding peptide conjugated to a DOTA chelator, originally discovered at the University of Heidelberg and developed by Germany-based 3B Pharmaceuticals (3BP). Novartis acquired global exclusive rights to 3BP's FAP-targeting peptide technology — including FAP-2286 — in a deal valued at up to USD 425 million announced in April 2023, following an earlier license held by Clovis Oncology. The head-to-head design of Part 2 is therefore less a competitive comparison than an internal benchmarking exercise: Novartis appears to be evaluating whether DFC413 offers imaging performance that justifies its development alongside, or potentially instead of, the more established NNS309 tracer.