A Single-arm, Single-center, Phase II Clinical Study of AK112 (a Dual-specific Antibody Against PD-1/VEGF) Combined With Hepatic Arterial Infusion Chemotherapy (HAIC) for the Treatment of Unresectable Hepatocellular Carcinoma.

This study is a single-center, open-label Phase II clinical trial, planning to enroll approximately 30 Chinese subjects with unresectable BCLC stage B or C hepatocellular carcinoma (HCC). The primary objective is to evaluate the safety and efficacy of AK112 (a dual-specific antibody against PD-1/VEGF) in combination with hepatic arterial infusion chemotherapy (HAIC) for the treatment of unresectable hepatocellular carcinoma.

All enrolled subjects will receive AK112 (20mg/kg Q3W) in combination with HAIC (utilizing the FOLFOX chemotherapy regimen) until the investigator determines no further clinical benefit (based on RECIST v1.1 imaging assessment and clinical evaluation), intolerable toxicity, completion of 24 months of treatment, or meeting other criteria for treatment discontinuation as outlined in the protocol, whichever comes first.

The study consists of screening period (up to 28 days from subject signing informed consent form to the first dose), treatment period (including treatment visits during treatment and end-of-treatment visit), and follow-up period (including safety follow-up visits, disease progression follow-up visits, and survival follow-up). Subjects will undergo screening assessments within 28 days before the first dose to determine their eligibility for the study.

All subjects will undergo regular tumor response assessments, with objective response rate (ORR) evaluated by the investigator according to RECIST v1.1 and mRECIST criteria as the primary efficacy endpoint. Within the first 48 weeks after the initial dose, tumor assessments will be conducted every 6 weeks (±7 days), and after 48 weeks, assessments will be performed every 12 weeks (±7 days). If a subject discontinues study treatment for reasons other than disease progression or death, tumor assessments should continue according to a fixed schedule until radiographic progression or termination of study treatment (whichever occurs first), initiation of new anti-tumor therapy, loss to follow-up, death, withdrawal of informed consent, or study closure, whichever occurs first. Confirmation of objective response should occur at least 4 weeks after the initial documentation of response, and in cases of clinical stability, confirmation assessments can be performed at the next scheduled time point.

Adverse events (AEs) will be followed up to 30 days after the last dose or initiation of new anti-tumor therapy, whichever occurs first. Serious adverse events (SAEs) will be followed up to 90 days after the last dose or initiation of new anti-tumor therapy, whichever occurs first. Survival assessments will be conducted every 3 months after the last dose, and information on subsequent anti-tumor therapy will be collected after termination of study treatment.