e16172 Background: Surufatinib is a selective inhibitor of VEGFRs, FGFR1, and CSF-1R, demonstrating dual mechanisms of anti-angiogenesis and immunomodulation. Combination therapy with anti-PD-1/PD-L1 antibodies may yield synergistic therapeutic effects. Methods: This single-arm, open-label, multicenter phase II clinical trial (NCT05282433) enrolled patients aged 18-75 years with unresectable hepatocellular carcinoma, BCLC stage B or C, and Child-Pugh class A or B liver function. Patients in Cohort 1 received surufatinib (250 mg orally once daily in 3-week cycles) combined with an anti-PD-1/PD-L1 antibody (administered every 3 weeks) as second-line therapy. Patients in Cohort 2 received surufatinib monotherapy (300 mg orally once daily in 3-week cycles) as third-line therapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: As of April 30, 2025, Cohort 1 enrolled 25 patients (median age 54 years; 20.0% female; 100% BCLC stage C; Child-Pugh A: 84.0%, B: 12.0%, C: 4.0%; 88.0% with elevated AFP, of which 60.0% had AFP ≥400 μg/L; 56.0% with vascular invasion; 88.0% with extrahepatic metastasis). Cohort 2 enrolled 18 patients (median age 58.5 years; 88.9% male; 100% BCLC stage C; 100% Child-Pugh A; 66.7% with elevated AFP, of which 38.9% had AFP≥400μg/L; 50.0% with vascular invasion; 72.2% with extrahepatic metastasis). In Cohort 1, three patients experienced rapid disease progression and discontinued study after only one cycle of immunotherapy, and two patients were not evaluable for efficacy. The ORR and DCR were 8.7% and 69.6%, respectively. The median PFS and median OS were 3.33 months and 7.36 months, respectively. The 16-week PFS rate was 40.0%, with 6-month and 12-month OS rates of 72.0% and 25.0%. In Cohort 2, one patient was not evaluable for efficacy. The ORR and DCR were 5.9% and 82.4% , respectively. The median PFS and median OS were 3.22 months and 13.60 months, respectively. The 16-week PFS rate was 50.0%, with 6-month and 12-month OS rates of 72.2% and 47.1%. Grade ≥3 treatment-related adverse events consisted primarily of thrombocytopenia and leukopenia. No new safety signals were identified. Conclusions: Surufatinib demonstrated promising efficacy and a manageable safety profile in patients with advanced hepatocellular carcinoma. Further studies in broader populations are warranted to validate these findings. Follow-up is ongoing, and additional data are anticipated. Clinical trial information: NCT05282433 .
Yang et al. (Thu,) studied this question.