A Phase I Dose Escalation And Cohort Expansion Study Of T-Cell Redirecting Bispecific Antibody Against Glypican 3 In Patients With Advanced Solid Tumors

TPS2592Background: Despite recent advance of immunotherapy, not all patient benefit. Reasons for the limited therapeutic effect include a low level of target protein expression or tumor immunogenicity. Bispecific antibodies to engage T-cells onto tumor are one approach to more active immunotherapy. However, management of on target/off tumor adverse effects including cytokine release can be a challenge. Glypican 3 (GPC3) is expressed across variety of solid tumors including hepatocellular carcinoma, while its expression in normal tissue is limited, making it an ideal target for a bispecific antibody. Our T-cell redirecting bispecific antibody against GPC3 is a fully humanised IgG4 bispecific antibody to recognise GPC3 on tumor with mutation to silence FcγR. Preclinical data show that this antibody is highly active against variety of GPC3-positive tumors, including poorly immunogenic models. Utilizing corticosteroids was effective in reducing cytokine release and widens the therapeutic window in preclinical...