Phase 1/2a VBC108 CLDN18.2×CDH17 bispecific topo1 inhibitor ADC in advanced solid tumors.

This first-in-human, multicenter, open-label Phase 1/2a study tests VBC108, a CLDN18.2- and CDH17-directed bispecific antibody-drug conjugate from VelaVigo Bio that delivers a topoisomerase I inhibitor payload to antigen-expressing tumor cells. Phase 1 uses Bayesian optimal interval (BOIN) dose escalation to define the maximum tolerated dose and/or recommended Phase 2 dose, with potential backfill cohorts; Phase 2a then dose-optimizes and expands into selected solid-tumor cohorts to further characterize safety and preliminary efficacy. The dual-target concept is aimed at gastrointestinal malignancies where antigen heterogeneity can drive escape, leveraging CDH17 (enriched in GI-lineage tumors) alongside CLDN18.2 (frequent in gastric/GEJ and some pancreatic cancers) to broaden on-tumor binding. Patients have unresectable, advanced/metastatic solid tumors, a setting where care is typically sequential systemic therapy (platinum/fluoropyrimidine- or gemcitabine-based chemo depending on histology) plus biomarker-directed options (HER2-, FGFR2-, CLDN18.2-, MSI-high/TMB-high-, or PD-L1–guided immunotherapy) when present. Commercially, this is an early read on whether bispecific “OR-gate” tumor targeting can improve ADC coverage without giving up potency from a topo1i payload.