Ivonescimab (PD-1/VEGF bispecific antibody) combined with HAIC for first-line treatment of unresectable hepatocellular carcinoma (uHCC): A prospective, single-arm phase II study.

e16212 Background: The combination of systemic therapies and hepatic arterial infusion chemotherapy (HAIC) has shown promising results in treating unresectable hepatocellular carcinoma (uHCC). The integration of anti-angiogenesis agents with immune checkpoint inhibitors (ICIs) has become a common strategy for uHCC. Ivonescimab, a new tetravalent anti-PD-1/VEGF bispecific antibody, has demonstrated good safety and efficacy in several cancers. This study aims to evaluate the efficacy and safety of ivonescimab combined with HAIC as a first-line treatment for uHCC patients (pts). Methods: Eligible treatment-naive unresectable HCC pts with BCLC stage B or C were enrolled to receive ivonescimab (20 mg/kg, every 3 weeks) combined with HAIC (oxaliplatin 85 mg/m², leucovorin 200 mg/m², and fluorouracil 2400 mg/m²; every 3 weeks; up to 6 cycles). Treatment continued until disease progression, intolerable toxicity, or surgical resection occurred. The primary endpoint is the objective response rate (ORR) assessed by RECIST v1.1 and mRECIST criteria. Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), surgical conversion rate, overall survival (OS), and safety. Results: Between August 22, 2024, and December 31, 2024, 27 pts were enrolled. Among them, 12 pts underwent at least three treatment cycles and had at least one imaging assessment, with a median age of 63 years. Of these 12 pts, 33.3% were at BCLC stage C, 100% had HBV infection, 25.0% had portal vein tumor thrombosis (PVTT), and 8.3% exhibited extrahepatic spread. The ORR and DCR per RECIST v1.1 were 41.7% and 91.7%, respectively, while the ORR and DCR per mRECIST were 75.0% and 91.7%, respectively. The surgical conversion rate was 58.3%. All 27 pts were included in the safety analysis set. Treatment-related adverse events (TRAEs) were observed in 19 pts (70.4%), with most events being grade 1 or 2 and primarily attributed to HAIC. Grade 3 TRAEs were reported in 6 pts (22.2%), with the most frequent events being decreased platelet count (5 pts, 18.5%), decreased lymphocyte count (3 pts, 11.1%), and decreased white blood cell count (3 pts, 11.1%). Hyperbilirubinemia was observed in 1 patient (3.7%). Most grade 3 TRAEs were manageable and resolved without permanent discontinuation of therapy. Furthermore, no grade 4 TRAEs were identified. Conclusions: Ivonescimab combined with HAIC demonstrated promising clinical benefits and an acceptable safety profile in the first-line treatment of uHCC. These results warrant further evaluation in larger clinical trials. Clinical trial information: NCT06375486 .