Hepatic Artery Infusion Chemotherapy (HAIC) Combined with Apatinib and Camrelizumab for Hepatocellular Carcinoma (HCC) in BCLC Stage C: A Prospective, Single-Arm, Phase II Trial (TRIPLET Study)

4106 Background: The combination of anti-angiogenesis and immune checkpoint blockade has been proven to improve clinical outcomes of advanced HCC. We assessed the efficacy and safety of HAIC combined with apatinib and camrelizumab for BCLC stage C HCC. Methods: Consecutive treatment-naive patients with BCLC stage C HCC were enrolled in this phase II trial (NCT04191889). Eligible patients were administrated with HAIC (oxaliplatin 85 mg/m 2 , leucovorin 400 mg/m 2 and fluorouracil 2500 mg/m 2 ; q3w), combined with apatinib (250 mg qd) and camrelizumab (200 mg q3w) for 6 cycles, followed by maintenance therapy with apatinib and camrelizumab until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Following an optimal Simon 2-stage design, 26 eligible patients needed to be included in the first stage, of whom at least 11 patients had to achieve objective responses to warrant further investigation in the second stage. Results: In the first stage, confirmed ORR was achieved in 16 and 20 patients per RECIST v1.1 and mRECIST, respectively, therefore enrollment of the second stage continued. From 4/13/2020 to 1/31/2022, 31 eligible patients were enrolled and 29 evaluable for efficacy analyses. The 31 patients were characterized with median age 45 years (range 30-67), men 96.77%, Child-Pugh A 100%, portal vein tumor thrombus Vp 1-2/Vp 3-4 25.81%/45.16%, and extrahepatic metastasis 12.90%. As of 1/31/2022, with a median follow-up of 18.07 months (95% CI 14.10 to 22.04), the confirmed ORR was 70.96% (95% CI, 53.41%-83.91%) with 22 partial responses (PR) per RECIST v1.1,while 87.10% (95% CI, 71.15%-94.87%) with 3 (9.68%) complete responses (CR) and 24 (77.42%) PR per mRECIST. The disease control rate (DCR) was 87.10% (95% CI, 71.15%-94.87%) whether per RECIST v1.1 or mRECIST. The median time to response (TTR) was 2.67 months (interquartile range (IQR), 1.43-2.96) per RECIST v1.1 and 2.03 months (IQR, 1.37-2.80) per mRECIST. The median progression-free survival (PFS) time was 9.37 months (95% CI 7.00 to 11.73) per RECIST v1.1 and 9.63 months (95% CI 5.82 to 13.44) per mRECIST, in particular, the liver-specific median PFS time was 10.80 months (95% CI 5.88 to 15.72) per mRECIST. The 6-month, 12-month, and 18-month overall survival rate were 93.1%, 85.8%, and 65.8%, respectively. Grade ≥3 adverse events (AEs) occurred in 74.19% of the patients, of which the most common AEs were decreased neutrophils (52.17%), decreased lymphocytes (43.38%), and increased ALT and AST (30.43% and 43.48% for each). Conclusions: The triplet treatment of HAIC, apatinib and camrelizumab showed promising clinical benefits and acceptable safety for BCLC Stage C HCC. Further confirmatory randomized controlled trial is about to get underway. Clinical trial information: NCT04191889.