Clinical studies have shown that combination therapy of PD-1 and VEGF antibodies significantly improves clinical benefit over PD-1 antibody alone in certain settings. Ivonescimab, an on-market tetravalent anti-PD-1/VEGF bispecific antibody, was designed to improve efficacy and safety over combo therapy. In this study, the mechanism of action is investigated. In the presence of VEGF, ivonescimab forms soluble complexes with VEGF dimers, leading to the enhanced binding avidity of ivonescimab to PD-1 therefore promoting its increased potency on PD-1/PD-L1-signaling blockade.