Development and validation of an antidrug antibody assay for TRK-950 using Melon™ gel and SPEAD pretreatment.

AIM & METHODS: TRK-950, a humanized IgG1 monoclonal antibody against CAPRIN-1, which is reported to be expressed on the cell surface of various forms of cancer, is currently being developed for multiple types of solid cancer. We developed an antidrug antibody (ADA) assay that includes two pretreatment processes for use in clinical trials, namely, Melon™ gel treatment and solid-phase extraction with acid dissociation (SPEAD), to reduce baseline variability between individual serum samples and improve drug tolerance. RESULTS: Comparing the assay with or without the pretreatment process using commercially available human serum samples, the mean response calculated from 18 individual human samples decreased from 327 to 270, and the coefficient of variation decreased from 41% to 16%. The new assay with the two-step pretreatment met the criteria set by the regulatory agency throughout the validation study. We also confirmed the recovery rates of IgG, IgM, and ADA - drug immune complexes after treatment with Melon™ gel. Clinical trials (NCT05423262) employing this improved analytical method have been conducted, and the results confirm the low immunogenicity of TRK-950. CONCLUSION: The combination of pretreatment with Melon™ gel and SPEAD is applicable for clinical ADA assays.