For a study, researchers sought to couple baseline blood cytokine measurements using bead-based multiplex immunoassay with multiplex immunofluorescence on tissue specimens to uncover novel markers of responsiveness to VEGF/PD-1 combo therapy in HCC. Sintilimab, an anti-PD-1 drug, and IBI305, a biosimilar to bevacizumab, were used in this research to treat patients with advanced hepatocellular carcinoma (HCC). IBI305 (7.5 or 15 mg/kg) and sintilimab (200 mg) were administered every 3 weeks to 50 patients with advanced HCC as a part of a phase Ib clinical trial. Of the total responders, 34.0% (17/51) finished the survey. Overall survival (OS) and progression-free survival (PFS) medians were 10.5 and 20.2 months, respectively. The incidence of grade 3 to 5 adverse events was decreased in the 7.5 mg/kg (13.8%) dosing group compared to the 15 mg/kg (28.6%) treatment group. Clinical benefit (CB) patients had blood CD137 values that were considerably higher than those of non-CB patients, according to biomarker studies (median, 32.8 pg/mL vs. 19.8 pg/mL, P=0.034). When compared to patients with low CD137 levels, patients with high levels had a considerably longer PFS (median, 14.2 months vs. 4.1 months, P=0.001). A larger number of M1 macrophages (CD68+CD163) in the stroma was similarly linked with enhanced efficacy (P=0.033) and prolonged PFS (P=0.024). Sintilimab with IBI305 was a well-tolerated and successful treatment for advanced HCC. Other predictive factors included the existence of M1 macrophage tumor infiltration and serum CD137 levels.