lutetium Lu 177 rofapitide tetraxetan (AAA614)

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.

Lu-FAP-2286 PTRT, applied in a broad spectrum of cancers, was relatively well-tolerated with acceptable side effects and demonstrated long retention of the radiopeptide. Prospective clinical studies are warranted.

Legal entity responsible for the study: Clovis Oncology, Inc., 3B Pharmaceuticals GmbH. Funding: Clovis Oncology, Inc., 3B Pharmaceuticals GmbH.