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

NCT07487662 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: ACTION-001IIT-2026-010
• Study Type: interventional
• Target: 105
• Locations: 0 countries
• Sites: N/A

Brief 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. 1.TACE or ablation combined with anti-CTLA-4 and anti-PD-1 immunotherapy;
2. 2.TACE or ablation combined with anti-CTLA-4 + anti-PD-1 + lenvatinib;
3. 3.Dual immunotherapy with anti-CTLA-4 and anti-PD-1;
4. 4.Anti-CTLA-4 + anti-PD-1 + lenvatinib. Efficacy differences between groups will be compared using Bayesian statistical methods based on non-informative priors.

Conditions

Hepato Cellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• 1-year recurrence-free survival rate

  The proportion of subjects who did not experience tumor recurrence or death within 1 year after surgery.

  One year

Secondary Outcomes (3)

• major pathological response rate, MPR rate

  5 weeks

• Objective response rate, ORR

  5 weeks

• Adverse Events, AE

  One year

Study Arms (5)

TACE/ablation+ anti-CTLA-4+anti-PD-1 therapy

EXPERIMENTAL

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.

Drug: sintilimab; Drug: ipilimumab N01; Procedure: TACE; Procedure: ablation

TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib therapy

EXPERIMENTAL

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.

Drug: sintilimab; Drug: ipilimumab N01; Drug: Lenvatinib; Procedure: TACE; Procedure: ablation

anti-CTLA-4+anti-PD-1 therapy

EXPERIMENTAL

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.

Drug: sintilimab; Drug: ipilimumab N01

anti-CTLA-4+anti-PD-1+lenvatinib therapy

EXPERIMENTAL

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.

Drug: sintilimab; Drug: ipilimumab N01; Drug: Lenvatinib

Surgery alone

NO INTERVENTION

Patients in this trial arm will undergo resection within 7 days after randomization, followed by regular postoperative follow-up.

Interventions

sintilimab DRUG

200mg ivdrip q3w

TACE/ablation+ anti-CTLA-4+anti-PD-1 therapy; TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib therapy; anti-CTLA-4+anti-PD-1 therapy; anti-CTLA-4+anti-PD-1+lenvatinib therapy

ipilimumab N01 DRUG

3mk/kg ivdrip q3w

TACE/ablation+ anti-CTLA-4+anti-PD-1 therapy; TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib therapy; anti-CTLA-4+anti-PD-1 therapy; anti-CTLA-4+anti-PD-1+lenvatinib therapy

Lenvatinib DRUG

8mg P.O QD

TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib therapy; anti-CTLA-4+anti-PD-1+lenvatinib therapy

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.

TACE/ablation+ anti-CTLA-4+anti-PD-1 therapy; TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib 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.

TACE/ablation+ anti-CTLA-4+anti-PD-1 therapy; TACE/ablation+ anti-CTLA-4+anti-PD-1+lenvatinib therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) 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;
• \) No prior tumor-related treatment received;
• \) At least one measurable target lesion according to the RECIST 1.1 criteria;
• \) ECOG PS score of 0-1;
• \) Liver function classification: Child-Pugh Class A;
• \) Estimated survival time ≥ 12 weeks;
• \) Hematological, liver, and renal functions meet the following criteria:
• Hemoglobin concentration ≥ 90 g/L;
• Neutrophil count ≥ 1.5 × 10⁹/L;
• Platelet count ≥ 75 × 10⁹/L;
• Total bilirubin ≤ 1.5 × ULN (Upper Limit of Normal);
• AST and ALT \< 5 × ULN; ALP \< 4 × ULN;
• Creatinine ≤ 1.5 × ULN;
• INR ≤ 1.5 × ULN; APTT ≤ 1.5 × ULN;
• Serum albumin concentration ≥ 30 g/L;

You may not qualify if:

• \) Prior history of HCC treatment; 2) Tumor rupture and bleeding, or suspected peritoneal metastasis;
• \) History of other complex surgeries within 6 weeks;
• \) Prior history of organ transplantation;
• Currently receiving treatment in other clinical trials;
• \) Prior history of autoimmune diseases, inflammatory disorders (such as inflammatory bowel disease, etc.), diverticulitis, systemic lupus erythematosus, sarcoidosis syndrome, Wegener's syndrome (granulomatosis with polyangiitis, rheumatoid arthritis, etc.), except for the following cases: vitiligo or alopecia areata, hypothyroidism with stable condition after drug replacement therapy, chronic skin diseases that do not require systemic treatment, and celiac disease controllable by diet alone;
• \) Prior history of allergy to anti-PD1 drugs or anti-CTLA4 drugs, or allergy to chemical molecules similar to the above drugs, or prior severe allergic reaction to other monoclonal antibodies;
• \) Uncontrollable intermittent recurrent diseases, including but not limited to: persistent infections (including tuberculosis), hypertension uncontrollable by drugs (\> 140/90 mmHg), interstitial lung disease, severe chronic gastrointestinal diseases complicated with diarrhea, mental illness or social disorders that cannot comply with clinical research requirements, factors with high risk of side effects, and inability to sign the informed consent form;
• \) Patients with prior hepatic encephalopathy, refractory ascites, or esophagogastric varices with high bleeding risk; patients with upper gastrointestinal bleeding within 1 year before the first administration;
• \) Untreated active hepatitis B subjects (HBsAg positive and HBV-DNA exceeding 5000 copies/mL (1000 IU/mL) or higher than the lower limit of detection, whichever is higher); for subjects with hepatitis B, anti-hepatitis B virus treatment is required during the study treatment; active hepatitis C subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection);
• \) Patients with primary brain tumors (except meningiomas or other benign brain tumors), or any brain metastases, leptomeningeal carcinomatosis, epilepsy uncontrollable by conventional drugs, or new-onset stroke within 1 year;
• \) Primary immunodeficiency disease;
• \) Prior positive HIV test or acquired immunodeficiency syndrome (AIDS);
• \) Use of immunosuppressive drugs within 14 days before the start of study treatment. The following situations are exempt:
• 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);

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Related Publications (3)

• 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.

  PMID: 41125112 RESULT

• 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.

  PMID: 33510460 RESULT

• 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: clinicalguidelines@esmo.org. 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.

  PMID: 39986353 RESULT

MeSH Terms

Interventions

sintilimab; lenvatinib

Central Study Contacts

Ming Ming

CONTACT

+86 020-87755766; kuangm@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2026
• First Posted: March 23, 2026
• Study Start: March 18, 2026
• Primary Completion (Estimated): March 17, 2028
• Study Completion (Estimated): March 17, 2028
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share