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

Conditions

• Hepato Cellular Carcinoma (HCC)

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• sintilimab — DRUG
  200mg ivdrip q3w
• ipilimumab N01 — DRUG
  3mk/kg ivdrip q3w
• Lenvatinib — DRUG
  8mg P.O QD
• TACE — PROCEDURE
  TACE 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
  Ablation 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.

Study Details

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.

Key Dates

Start date

Mar 18, 2026

Status verified

Mar 2026

Primary completion

Mar 17, 2028

Completion

Mar 17, 2028

Study Design

Enrollment

105 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: TACE/ablation+ anti-CTLA-4+anti-PD-1 therapy
  Patients in this trial group will receive two cycles of neoadjuvant therapy with sintilimab combined with ipilimumab N01, administered every 3 weeks (q3w). One week after the first cycle of treatment, the multidisciplinary team (MDT) will determine to perform either TACE or ablation according to the lesion status. Surgical treatment will be performed 2 weeks after the completion of the second cycle of neoadjuvant drug therapy. Adjuvant therapy with sintilimab will be initiated 4 weeks postoperatively, given every 3 weeks for a maximum of 15 cycles.
• Experimental: TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib therapy
  Patients in this trial group will receive two cycles of neoadjuvant therapy with sintilimab combined with ipilimumab N01 and lenvatinib, administered every 3 weeks (q3w). One week after the first cycle of treatment, the multidisciplinary team (MDT) will determine to perform either TACE or ablation according to the lesion status. Surgical treatment will be performed 2 weeks after the completion of the second cycle of neoadjuvant drug therapy. Adjuvant therapy with sintilimab and lenvatinib will be initiated 4 weeks postoperatively, given every 3 weeks for a maximum of 15 cycles.
• Experimental: anti-CTLA-4+anti-PD-1 therapy
  Patients in this trial group will receive two cycles of neoadjuvant therapy with sintilimab combined with ipilimumab N01, administered every 3 weeks (q3w). Surgical treatment will be performed 2 weeks after the completion of the second cycle of neoadjuvant drug therapy. Adjuvant therapy with sintilimab will be initiated 4 weeks postoperatively, given every 3 weeks for a maximum of 15 cycles.
• Experimental: anti-CTLA-4+anti-PD-1+lenvatinib therapy
  Patients in this trial group will receive two cycles of neoadjuvant therapy with sintilimab combined with ipilimumab N01 and lenvatinib, administered every 3 weeks (q3w). Surgical treatment will be performed 2 weeks after the completion of the second cycle of neoadjuvant drug therapy. Adjuvant therapy with sintilimab and lenvatinib will be initiated 4 weeks postoperatively, given every 3 weeks for a maximum of 15 cycles.
• No Intervention: Surgery alone
  Patients in this trial arm will undergo resection within 7 days after randomization, followed by regular postoperative follow-up.

Primary Outcome Measure

1-year recurrence-free survival rate [ Time Frame: One year ]

Central Contacts

• Ming Ming
  +86 020-87755766
  [email protected]