GCT1042-01: A First-in-Human, Open-label, Dose-escalation Trial with Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects with Malignant Solid Tumors

GEN1042 is a bispecific antibody that crosslinks CD40 on antigen-presenting cells with 4-1BB on activated T cells, thereby inducing conditional stimulation of and co-stimulatory activity on both cell types. It is hypothesized that upon simultaneous binding of GEN1042 to CD40 on
dendritic cells and 4-1BB on T cells, the CD40-binding arm induces dendritic cell licensing through CD40 cross-linking, which together with cross-linking of 4-1BB by the other arm, leads to efficient, conditional T-cell activation. Since resting T cells lack 4-1BB expression, T cells will only be activated by GEN1042 after T-cell receptor triggering. In the context of cancer, GEN1042 is hypothesized to enhance anti-tumor immunity by cross-linking 4-1BB-positive, tumor-specific T cells with CD40-positive antigen-presenting cells in either the tumor-draining lymph nodes or intratumorally.