JS207（一种靶向PD-1和VEGF-A的双特异性抗体）联合JS007（抗CTLA-4）治疗晚期肝细胞癌患者的随机、多中心II期研究

Purpose JS207 is a bispecific antibody targeting PD-1 and VEGF-A. This Phase II study (NCT06954467) aimed to evaluate the safety and efficacy of JS207 in combination with JS007, an antibody targeting CTLA-4, in patients with advanced hepatocellular carcinoma (HCC). Methods This study comprised a dose exploration phase with 3 to 12 patients for selection of the optimal dose of JS007, followed by a randomized expansion phase enrolled 40 to 60 patients. Patients with histologically or cytologically confirmed unresectable or metastatic HCC who had not previously received any systemic anticancer therapy were eligible. In the dose exploration phase, a fixed dose of JS207 at 10 mg/kg was administered every 3 weeks (Q3W) in combination with JS007. In the first dose cohort, patients received a single dose of JS007 at 3 mg/kg on cycle 1 day 1, then 1 mg/kg Q6W beginning at cycle 4. Depending upon the tolerability in this first dose cohort, JS007 was to be escalated to 3 mg/kg Q6W or de-escalated to 1 mg/kg Q3W for the first 4 cycles, followed by JS007 1 mg/kg Q6W beginning at cycle 4 in both the escalated and de-escalated cohorts. Based on the dose exploration phase, the optimal JS007 dose regimen was selected for use in the randomized expansion phase. During the randomized (1:1) expansion phase, patients were assigned to receive either JS207 10 mg/kg Q3W combined with JS007 or JS207 10 mg/kg Q3W as monotherapy. The primary endpoints included safety and investigator-assessed objective response rate (ORR). Results As of December 15, 2025, 10 patients were enrolled in the dose exploration phase. Three patients received JS207 in the initial dose cohort, while 7 patients received JS207 combined with JS007 in the higher dose cohort (3 mg/kg Q6W x 4 cycles, then 1 mg/kg Q6W thereafter). No patients experienced dose-limiting toxicity. The most common treatment-related adverse events (TRAEs) (incidence ≥ 20%) included increased alanine aminotransferase (50.0%), increased aspartate aminotransferase (50.0%), anaemia (50.0%), pyrexia (40.0%), thrombocytopenia (40.0%), hypothyroidism (30.0%), proteinuria (30.0%), rash (30.0%), and infusion related reactions (30.0%). Three patients (30.0%) experienced grade ≥ 3 TRAE; no patients experienced treatment-emergent adverse events leading to death. Among patients who reveived the initialor higher dose of JS007, the ORR were 33.3% (1/3) and 71.4% (5/7), respectively. The disease control rate was 100% (3/3) and 85.7% (6/7), respectively. Conclusion The combination of JS207 and JS007 demonstrated promising efficacy with an acceptable safety profile as first line treatment of advanced HCC. The randomized expansion phase of this study is ongoing.