TACE or Ablation Combined With Sintilimab and Ipilimumab N01 as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With Intermediate-High Recurrence Risk

Summary

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.

Timeline

Start

2026-03-18

Primary completion

2028-03-17

Completion

2028-03-17

Publications

• Results Wang Z, Fan J, Zhou S, Sun Y, Liang F, Ji Y, Gu F, Li T, Peng L, Peng T, Huang X, Ding Z, Bai D, Xiang B, Tan G, Wen T, Zeng Y, Han F, Zhang Y, Wu S, Zhao H, Chen Y, Shi G, Hou Z, Sun Y, Zhu W, Zhou J. Perioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): a randomised phase 2/3 trial. Lancet. 2025 Nov 1;406(10515):2089-2099. doi: 10.1016/S0140-6736(25)01720-9. Epub 2025 Oct 19.
• Results Llovet JM, De Baere T, Kulik L, Haber PK, Greten TF, Meyer T, Lencioni R. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021 May;18(5):293-313. doi: 10.1038/s41575-020-00395-0. Epub 2021 Jan 28.
• Results Vogel A, Chan SL, Dawson LA, Kelley RK, Llovet JM, Meyer T, Ricke J, Rimassa L, Sapisochin G, Vilgrain V, Zucman-Rossi J, Ducreux M; ESMO Guidelines Committee. Electronic address: [email protected]. Hepatocellular carcinoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2025 May;36(5):491-506. doi: 10.1016/j.annonc.2025.02.006. Epub 2025 Feb 20. No abstract available.

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Indications