lutetium Lu 177 rofapitide tetraxetan (AAA614)

In our in vitro and in vivo studies, [177Lu]Lu-FAP-2286 and [161Tb]Tb-FAP-2286 demonstrated similar behavior. In the applied PDAC mouse model, FAP-TRT showed limited therapeutic efficacy, most likely due to the limited radiopharmaceutical uptake observed in the tumors. This hampered determination of a potential benefit of either radioisotope for FAP-TRT. Of note, a modest response was observed in the tandem therapy group that first received [177Lu]Lu-FAP-2286, followed by [161Tb]Tb-FAP-2286.

Particularly small molecules (i.e. FAPI-46, FAPI-74) and peptides (i.e. FAP-2286, DOTAGA.SA.FAPi) seem to be some of the most promising molecular probes for imaging and therapy...In contrast, FAP-targeted therapeutics remain in the Phase-I or proof-of-concept stage but brings hope for patients with systemic disease who are left out and urgently need additional innovation drives beyond the standard care. This review article will give insight into the most recent developments in the FAP-Therapeutic applications of cancer treatments using several different promising FAP-derivates to improve FAP-theranostic in oncology.

Quantitative parameters derived from [68Ga]Ga-FAP-2286 PET/CT are valuable predictors of [177Lu]Lu-FAP-2286 treatment efficacy in NSCLC patients. Dynamic monitoring of these metrics allows for early identification of treatment responses and supports personalized therapy strategies.

Squaric acid derivatization synergistically elevates affinity, hydrophilicity, and intratumoral residence while preserving safety, establishing 68Ga/177Lu-FAP2286-SA as a clinically translatable, next-generation theranostic pair for FAP-positive malignancies.

177Lu-FAP-2286 demonstrated good feasibility and safety in treating FAP-positive gastrointestinal tumors, resulting in disease stabilization in a subset of patients.

P=N/A, N=30, Recruiting, The affiliated hospital of southwest medical university; The affiliated hospital of southwest medical university

P2, N=10, Not yet recruiting, Ankara University

177Lu-OncoFAP and 177Lu-FAP-2286 were included in the biodistribution study as controls. OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of 177Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors.

P1/2, N=222, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

P1/2, N=222, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1/2, N=300, Recruiting, Clovis Oncology, Inc. | N=170 --> 300

FAP-targeted radiopharmaceutical enhances PD-1-antibody-mediated TGI by increasing recruitment of tumor-infiltrating CD8+ T cells, which is enhanced and maintained in the presence of anti-PD-1. These findings provide a rationale for clinical studies of combined 177Lu-FAP-2286 radiotherapy and immune checkpoint blockade in FAP-positive tumors.