Background
Type I insulin-like growth factor receptor (IGF-1R) is a transmembrane protein which is overexpressed in solid tumors including non–small cell lung, prostate, sarcomas, and breast cancers.
[225Ac]-FPI-1434 is a radioimmunoconjugate consisting of a humanized monoclonal antibody (AVE1642) that binds to the external domain of IGF-1R, a proprietary bifunctional chelate, and the alpha-emitting radionuclide actinium-225 (Ac-225). Internalization of the radioimmunoconjugate and decay of Ac-225 causes tumor cell death primarily through double stranded DNA breaks. The indium-111 analog, [111In]-FPI-1547, with the identical antibody and bifunctional chelate is used for patient selection and quantification of IGF-1R expressing targets prior to therapy.
Based on anti-tumor activity of [225Ac]-FPI-1434 in non-clinical models, favorable toxicology studies in cynomolgus monkeys, and prior human experience with the unconjugated antibody, the first-in-human trial was initiated.
