Cryoablation combined with camrelizumab and apatinib in advanced hepatocellular carcinoma: A prospective, single-arm, phase II study.

e16229 Background: Anti-angiogenesis agents plus immune checkpoint inhibitors have been established as the first-line therapy for advanced hepatocellular carcinoma (aHCC). However, a relatively high proportion of aHCC patients haven shown resistance to these treatment regimens. Tumor ablation, particularly cryoablation, may inactivate tumor tissue locally, releasing the tumor-related proteins and potentially inducing an abscopal effect. Few studies have explored whether cryoablation can enhance the efficacy of these agents. Therefore, this study aimed to evaluate the efficacy and safety of combining cryoablation with apatinib and camrelizumab in aHCC patients. Methods: This study aimed to recruit 27 patients with advanced HCC, and 7 patients have been enrolled thus far. The main inclusion criteria are as follows: aged 18-70 years; pathologically confirmed diagnosis of HCC; CT/MRI diagnosed portal vein tumor thrombus (PVTT); the sum of the number and maximum diameter of intrahepatic lesions not exceeding 7 cm; no previous anticancer treatment; Child-Pugh grade A. Patients were treated with cryoablation to inactivate lesions as much as possible. Within 48 hours of cryoablation, they received camrelizumab (200mg, intravenous infusion, q3w) and apatinib (250mg, orally, qd) for a maximum of 2 years, disease progression or unacceptable adverse events occurred. The primary endpoint was the objective response rate (ORR), assessed using mRECIST v1.1/mRECIST). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: All patients in the study were male, and all were infected with hepatitis viruses (HBV 100%, HCV 14.3%). Vp3/4 PVTT was present in 57.1% of patients. Three patients were diagnosed with extrahepatic metastasis. Five patients reached the study endpoint (3 for disease progression, 1 for withdrawing informed consent, and 1 for intolerable adverse effects). Six patients (38%) had extrahepatic metastasis. With a median follow-up of 15.6 months (IQR: 6.33-18.8), the ORRs were 71.4% per mRECIST and 14.3% per RECISTv1.1. The median PFS (mRECIST) and OS were 4.63 months and 19.0 months, respectively. The most common adverse events were hypertension (42.9%) and proteinuria (42.9%). No treatment-related serious adverse events were observed. Conclusions: Cryoablation combined with apatinib and camrelizumab as the first-line strategy for aHCC patients with PVTT and below up-to-7 criteria demonstratebeld a promising value by improving ORR and OS with acceptable side effects. Clinical trial information: NCT04724226 . Baseline characteristics of patients. Couple group (N=7) Sex Male 7 (100%) Age Mean (SD) 54.6 (10.6) Maximum diameter of intrahepatic lesions Median [Q1,Q3] 6.10 [5.90,6.60] Etiology HBV 6 (85.7%) HBV & HCV 1 (14.3%) Child-Pugh score 5 5 (71.4%) 6 2 (28.6%) Type of PVTT Vp1 1 (14.3%) Vp2 2 (28.6%) Vp3 1 (14.3%) Vp4 3 (42.9%)