Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The recurrence rate after curative resection for early-stage HCC remains extremely high, with 2-year and 5-year recurrence rates reaching 50% and 70%, respectively. Currently, no standard perioperative treatment is recommended in domestic and international guidelines.
Recently, data from a phase III clinical study, investigating neoadjuvant and adjuvant therapy with camrelizumab plus apatinib in resectable HCC patients at intermediate-to-high risk of recurrence, demonstrated that the neoadjuvant and adjuvant therapy combining targeted therapy and immunotherapy could significantly reduce postoperative recurrence. The median recurrence-free survival (RFS) in the target-immunotherapy group was 42.1 months, which was remarkably longer than 19.4 months in the surgery-alone group.
Local therapies (TACE, ablation) can induce immunogenic cell death of tumors and remodel the tumor microenvironment, thereby exerting synergistic effects with immunotherapy. This strategy is expected to further improve recurrence-free survival in HCC patients after surgery.
This clinical trial aims to explore the efficacy and tolerability of the following regimens compared with surgery alone:
1. TACE or ablation combined with anti-CTLA-4 and anti-PD-1 immunotherapy; 2. TACE or ablation combined with anti-CTLA-4 + anti-PD-1 + lenvatinib; 3. Dual immunotherapy with anti-CTLA-4 and anti-PD-1; 4. Anti-CTLA-4 + anti-PD-1 + lenvatinib. Efficacy differences between groups will be compared using Bayesian statistical methods based on non-informative priors.
1) Age: 18-75 years old; 2) Patients with hepatocellular carcinoma (HCC) classified as CNLC stage Ib-IIIa (excluding patients with Vp3 and Vp4), and deemed resectable by multidisciplinary team (MDT) discussion;
Hemoglobin concentration ≥ 90 g/L;
Neutrophil count ≥ 1.5 × 10⁹/L;
Platelet count ≥ 75 × 10⁹/L;
1) Prior history of HCC treatment; 2) Tumor rupture and bleeding, or suspected peritoneal metastasis;
Intranasal, inhaled, topically used steroids or local steroid injections;
Systemic application of corticosteroids not exceeding the physiological dose (e.g., 10 mg/day prednisone or its equivalent);
Steroid application for the treatment of allergic reactions;
Parallel
sintilimab
Drug200mg ivdrip q3w
ipilimumab N01
Drug3mk/kg ivdrip q3w
Lenvatinib
Drug8mg P.O QD
TACE
Procedure/SurgeryTACE will be performed in accordance with the standard procedures of the respective medical centers.Based on the judgment of the MDT team, patients with at least one lesion amenable to complete ablation will receive ablation therapy.Patients without any lesion amenable to complete ablation will receive TACE therapy.
ablation
Procedure/SurgeryAblation will be performed in accordance with the standard procedures of the respective medical centers.Based on the judgment of the MDT team, patients with at least one lesion amenable to complete ablation will receive ablation therapy.Patients without any lesion amenable to complete ablation will receive TACE therapy.
1-year recurrence-free survival rate
The proportion of subjects who did not experience tumor recurrence or death within 1 year after surgery.
major pathological response rate, MPR rate
The proportion of patients with histologically confirmed tumor necrosis of more than 90% in the surgically resected specimens.
Objective response rate, ORR
The proportion of patients who achieve complete response (CR) and partial response (PR) in tumor assessment according to the RECIST 1.1 criteria after neoadjuvant therapy and before surgical resection.
Adverse Events, AE
The proportion of patients who experienced grade ≥3 hematological or non-hematological adverse events from the start of treatment to the end of follow-up.
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Sun Yat-sen University
Lead sponsor
Innovent Biologics (Suzhou) Co. Ltd.
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
