Apatinib and camrelizumab plus Intravenous FOLFOX or hepatic arterial infusion chemotherapy with FOLFOX for advanced HCC: A multicenter, prospective, randomized phase III trial.

TPS4193 Background: The combination of anti-angiogenesis and immune checkpoint blockade showed promising outcomes for advanced hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) combined with apatinib and camrelizumab could augment treatment efficacy in preliminary study. But HAIC has disadvantages such as technical limitations, expensive cost, impaired liver function and poor patient comfort. Results from our previous phase II trial (NCT05412589) demonstrate that the triplet treatment of Venous Infusional FOLFOX plus camrelizumab and apatinib showed inspiring antitumor activity and acceptable safety for CNLC stage Ⅲ HCC, especially in those with main portal trunk invasion (Vp4). These results encourage us to further compare the efficacy and safety of intravenous FOLFOX with apatinib and camrelizumab versus HAIC-FOLFOX with apatinib and camrelizumab as first-line treatment in advanced HCC. Methods: This multicenter, randomized, open-label, non-inferiority phase 3 study (NCT06172205) will enroll 192 patients. Essential criteria for patient inclusion encompassed: age between 18 and 75 years; a clinical diagnosis conforms to primary hepatocellular carcinoma (HCC); classification with in BCLC stage C; no prior anti-tumor treatment exposure; presence of at least one measurable tumor as per RECIST v1.1; ECOG performance status score of either 0 or 1; and a Child-Pugh A or B. Eligible patients were randomized (1:1) into two groups. Randomization is stratified by the presence of macrovascular invasion or extrahepatic metastasis (yes vs no), and baseline alpha-fetoprotein concentration (<400 ng/mL vs ≥400 ng/mL). There are 2 arms in the study: (1) Arm A: FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2,5-fluorouracil bolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 hours; q3w; up to 6 cycles) intravenously in combination with apatinib (250 mg po qd) and camrelizumab (200 mg iv q3w). (2) Arm B: hepatic arterial infusion FOLFOX (oxaliplatin, leucovorin and 5-fluorouracil q3w; up to 6 cycles), combined with apatinib (250 mg po qd) and camrelizumab (200 mg iv q3w). The primary endpoint is 6-month progression-free survival (PFS) rate according to RECIST v1.1. Secondary outcomes encompass the Objective response rate, Disease control rate, Duration of response, PFS, Overall survival (OS), along with 12-month PFS rate, 6-month and 12-month OS rates. The additional secondary endpoints include assessment of treatment-related adverse events. With the assumption of a median 6-month PFS rate of 85% in the Arm B and 71% in the Arm A (noninferiority margin, 14%), a total of 162 patients were required under a two-sided 5% significance level and 80% power. Allowing a dropout rate of 15%, we aimed to enroll 192 patients. The trial is currently screening eligible patients. Clinical trial information: NCT06172205 .