Lutetium (177 Lu) Vipivotide Tetraxetan

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. The tumor types selected for this study are notable for their stromal density and historically high FAP expression: PDAC in particular is characterized by a pronounced desmoplastic stroma that has long been recognized as both a barrier to drug delivery and a potential imaging target. The inclusion of soft tissue sarcoma alongside the more common epithelial tumors reflects the known FAP expression in certain sarcoma subtypes and broadens the potential clinical utility of the imaging agent. The trial does not restrict enrollment by line of prior therapy, allowing patients across the treatment continuum, which maximizes the diversity of tumor biology captured in the imaging dataset. For Novartis, this trial fits within a coherent radioligand therapy strategy built around theranostic pairs — diagnostic agents that identify patients likely to respond to a matched therapeutic. The company’s approved radioligand therapy lutetium PSMA-617 (Pluvicto) for prostate cancer established this model commercially, and the FAP program represents an attempt to extend it into solid tumors where PSMA-targeted approaches are not applicable. Whether DFC413 ultimately advances as the companion diagnostic for the NNS309 therapeutic program, or serves a distinct role, will depend on the imaging concordance and biodistribution data generated in this study. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.

Japan-based PeptiDream Inc. (Tokyo Stock Exchange: 4587) has announced the first patient dosing in a first-in-human radiopharmaceutical clinical trial of 64Cu-PD-29875, a macrocyclic peptide conjugate targeting Claudin 18.2 (CLDN18.2) in patients with gastric or gastroesophageal junction (GEJ) cancer. The PeptiDream claudin18.2 radiopharmaceutical program is structured as a Phase 0 imaging study, using copper-64 (⁶⁴Cu) labelling to generate PET/CT imaging data on safety, pharmacokinetics, tumor uptake, and dosimetry. The study’s diagnostic data are intended to inform the development of a companion ²²⁵Ac-labeled therapeutic, forming an integrated radiotheranostic pair. Patient enrollment numbers and a projected completion date were not disclosed. Endpoints center on diagnostic performance characterization and dosimetry, with the imaging data expected to support the design of subsequent therapeutic trials. The program received funding from Japan’s Agency for Medical Research and Development (AMED) under its Practical Research for Innovative Cancer Control initiative in 2024. CLDN18.2 is a tight-junction transmembrane protein whose normal expression is tightly restricted to differentiated gastric epithelial cells, where it remains physically inaccessible to circulating agents. In gastric and GEJ cancer specifically, CLDN18.2 expression is retained through metastatic progression, making it relevant across disease stages rather than only at diagnosis. The clinical validation of this target arrived with the 2024 FDA approval of zolbetuximab-clzb (Vyloy), a CLDN18.2-directed monoclonal antibody from Astellas Pharma, in first-line HER2-negative, CLDN18.2-positive gastric/GEJ adenocarcinoma — the first approved therapy directed at this target. PD-29875 is a macrocyclic peptide discovered using PeptiDream’s proprietary Peptide Discovery Platform System (PDPS) technology and further optimized through in vivo imaging and efficacy studies at PDRadiopharma, PeptiDream’s wholly owned subsidiary. In its diagnostic configuration, the peptide is conjugated to ⁶⁴Cu, a positron emitter with a 12.7-hour half-life suited to the timescale of peptide biodistribution and tumor accumulation. The claudin18.2 PET imaging data generated in this Phase 0 study are designed to confirm tumor uptake, establish dosimetry parameters, and identify patients most likely to benefit from the therapeutic counterpart — a ²²⁵Ac-labeled version of the same peptide scaffold delivering targeted alpha-particle radiation. This theranostic strategy mirrors the PSMA paradigm in prostate cancer, where ⁶⁸Ga-PSMA PET imaging and ¹⁷⁷Lu-PSMA-617 (Pluvicto) therapy operate as a diagnostic-therapeutic pair. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.