A bridging assay for detection and characterization of anti-drug antibodies to dostarlimab, a new anti-PD-1 therapeutic monoclonal antibody
AbstractDostarlimab (JEMPERLI) is a humanized anti-programmed death 1 (PD-1) immunoglobulin (Ig)G4-kappa monoclonal antibody that binds to the PD-1 receptor and competitively inhibits binding of its ligands, PD-L1 and PD-L2. Dostarlimab was recently approved in the USA and the European Union. Because dostarlimab is a macromolecular therapeutic, it has the potential to elicit the formation of anti-drug antibodies, which have the capability to impact the drug’s safety and efficacy and to alter pharmacokinetics. The immunogenic potential of dostarlimab remains unknown, and it was therefore necessary to develop analytical assays to detect and characterize anti-drug antibodies as a key component in the mitigation of immunogenicity risk. Here, we present the development and optimization of a 3-tiered electrochemiluminescense bridging assay for the investigation of dostarlimab clinical immunogenicity. In this work, the full details of the method, statistical data analysis and cut point determinations, assay performance during clinical sample analysis, and associated regulatory expectations are discussed. The full validation of this 3-tier anti-drug antibody assay enabled dostarlimab immunogenicity evaluation in clinical studies. Trial registration: Clinicaltrials.gov, NCT02715284. Registered 9 March 2016
