An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against human epidermal growth factor receptor 3 (HER3; ErbB3) conjugated to a topoisomerase I (TopoI) inhibitor-based payload, with potential antineoplastic activity. Upon administration of anti-HER3/TopoI inhibitor ADC IBI133, the anti-HER3 antibody moiety targets and binds to HER3 expressed on tumor cells. Upon cellular uptake, the TopoI inhibitor inhibits DNA topoI activity, thereby inhibiting DNA replication which results in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of HER3-expressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors.