lutetium Lu 177 rofapitide tetraxetan (AAA614)

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.