Apatinib and camrelizumab plus hepatic arterial infusion with oxaliplatin and 5-fluorouracil vs. apatinib and camrelizumab as the first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A randomized multi-center clinical trial.

TPS4194 Background: The combination of immune checkpoint inhibitors and antiangiogenic drugs has been approved as the first-line treatment for advanced hepatocellular carcinoma (HCC). However, the survival benefit is still limited, especially in patients with high-risk features (Vp4, and/or bile duct invasion and/or tumor occupancy of ≥50% of the liver). Hepatic arterial infusion chemotherapy (HAIC) plus apatinib (an antiangiogenic drug) and camrelizumab (a PD-1 antibody) showed encouraging antitumor activity for these patients in a previous phase 2 study. Herein, we investigated the efficacy and safety of apatinib and camrelizumab plus HAIC compared with apatinib and camrelizumab as the first-line treatment for HCC with portal vein tumor thrombus (PVTT). Methods: In this randomized, open-label, phase 3 trial, eligible patients are ≥18 years with HCC confirmed by radiology, histology, or cytology. Other eligibility criteria were as follows: with PVTT, ECOG PS 0/1, no history of systemic therapy, not amenable to curative treatment approach, Child-Pugh A class liver score, and ≥1 measurable lesion by RECIST v1.1. A total of 214 patients (anticipated) will be randomized (1:1) to receive apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) plus HAIC with FOLFOX (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 , 5-fluorouracil bolus 400 mg/m 2 on day 1, and 5-fluorouracil infusion 2400 mg/m 2 for 20 hours via hepatic artery Q4W) or apatinib (250mg orally once daily) and camrelizumab (200 mg IV Q2W) until disease progression or intolerable toxicity. Stratification will be by patients with or without high-risk features. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, objective response rate per RECIST 1.1 and mRECIST, disease control rate per RECIST 1.1 and mRECIST, time to progression, duration of response, time to response, and safety. Whole-Exome Sequencing and RNA Sequencing of tumor biopsy samples were performed for predictive biomarker exploration. Clinical trial information: NCT05198609 .