Abstract
PEGylated biotherapeutics can elicit anti-PEG (polyethylene glycol) immune responses in patients treated with this category of drugs. While anti-PEG antibody assays for this class of biotherapeutics have become a common element of the clinical immunogenicity testing strategy, the overall antibody incidence induced by the nanoparticle (NP) delivery system (such as ACCURINS®) has not been fully studied to date. To support the immunogenicity assessment of one of Pfizer's NP-based therapeutics, consisting of gedatolisib (GEDA) encapsulated in ACCURINS® (GEDA-NP), we developed an anti-GEDA-NP antibody (ADA) assay on the MSD platform for the detection of GEDA-NP induced ADA in human serum. The focus of our strategy was on developing a clinically relevant ADA assay and systematically addressing assay interference through rigorous assay optimization. Our efforts led to a fit-for-purpose assay for the detection of anti-GEDA-NP ADA in serum samples obtained from breast cancer patients. Results from method qualification indicated robust assay performance, as highlighted by inter and intra-assay precision within 25% CV for all controls, and reproducible response profiles across multiple runs during the assessment of assay cut points with breast cancer samples. The assay sensitivity was between 4.3 ng/mL and 123 ng/mL for surrogate positive controls of IgG and IgM isotypes, respectively. Additionally, assay interference from nonspecific matrix proteins and circulating drug was addressed, which ensured accurate assessment of ADA incidence that can be attributed to GEDA-NP.