Hepato Cellular Carcinoma (HCC)Phase 2ACTION-001NCT07487662
TACE or Ablation Combined With Sintilimab and Ipilimumab N01 as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With Intermediate-High Recurrence Risk
A Phase 2 study testing sintilimab, ipilimumab N01 and Lenvatinib in people with Hepato Cellular Carcinoma (HCC), run by Sun Yat-sen University.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepato Cellular Carcinoma (HCC)
- What is being tested?
- sintilimab, ipilimumab N01 and Lenvatinib
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- No sites listed yet
- Study dates
- 18 Mar 2026to 17 Mar 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
- 3) No prior tumor-related treatment received;
- 4) At least one measurable target lesion according to the RECIST 1.1 criteria;
- 5) ECOG PS score of 0-1;
- 6) Liver function classification: Child-Pugh Class A;
- 7) Estimated survival time ≥ 12 weeks;
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- 8) 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;
- 9) Women of childbearing age must be excluded from pregnancy;
- 10) For patients with other concurrent malignant tumors, MDT discussion must confirm that the history and treatment history of other tumors will not interfere with the efficacy and safety evaluation of this study protocol;
- 11) Ability to understand and sign the informed consent form.
Who cannot join
- 1) Prior history of HCC treatment; 2) Tumor rupture and bleeding, or suspected peritoneal metastasis;
- 3) History of other complex surgeries within 6 weeks;
- 4) Prior history of organ transplantation;
- Currently receiving treatment in other clinical trials;
- 5) 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;
- 6) 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;
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- 7) 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;
- 8) 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;
- 9) 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);
- 10) 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;
- 11) Primary immunodeficiency disease;
- 12) Prior positive HIV test or acquired immunodeficiency syndrome (AIDS);
- 13) 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);
- Steroid application for the treatment of allergic reactions;
- 14) Vaccination with live-attenuated vaccines within 30 days before the start of study treatment. Note: Live-attenuated vaccines should also be avoided during the study treatment and within 30 days after the end of treatment;
- 15) Receipt of systemic immunostimulant treatment within the prior 4 weeks;
- 16) Prior history of severe systemic diseases, including: myocardial infarction or unstable angina pectoris, hypertensive crisis or hypertensive encephalopathy, congestive heart failure of NYHA Class II or above, unstable symptomatic arrhythmia requiring drug intervention, severe vascular disease or symptomatic peripheral vascular disease, occurring within 12 months before the start of study treatment;
- 17) History of coagulative, hemorrhagic or thrombotic diseases within 12 months before the start of study treatment;
- 18) Severe, irreversible trauma, ulcers or fractures;
- 19) Pregnant or lactating women, or subjects planning to have children during the trial period;
- 20) Dependent on parenteral nutrition to maintain life;
- 21) Other acute or chronic diseases, mental and psychological diseases, etc., which are not suitable for participating in this study, as judged by the researcher.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: TACE or Ablation Combined With Sintilimab and Ipilimumab N01 as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma With Intermediate-High Recurrence Risk: A Multicenter, Multigroup, Randomized, Phase Ⅱ Exploratory Clinical Trial
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.
Read more
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:
- TACE or ablation combined with anti-CTLA-4 and anti-PD-1 immunotherapy;
- TACE or ablation combined with anti-CTLA-4 + anti-PD-1 + lenvatinib;
- Dual immunotherapy with anti-CTLA-4 and anti-PD-1;
- 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)
- Being tested
- sintilimab, ipilimumab N01, Lenvatinib, TACE, ablation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sintilimabDrug
200mg ivdrip q3w
ipilimumab N01Drug
3mk/kg ivdrip q3w
LenvatinibDrug
8mg P.O QD
TACEProcedure or surgery
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.
ablationProcedure or surgery
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year recurrence-free survival rate
The proportion of subjects who did not experience tumor recurrence or death within 1 year after surgery.
Measured: One year
Secondary outcomes (3)
major pathological response rate, MPR rate
The proportion of patients with histologically confirmed tumor necrosis of more than 90% in the surgically resected specimens.
Measured: 5 weeks
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.
Measured: 5 weeks
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2026
- Study start18 Mar 2026 (estimated)
- Primary completion17 Mar 2028 (estimated)
- Study completion17 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepato Cellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Responsible party
- Principal investigator, Ming Kuang, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07487662
- Sponsor's protocol ID
- ACTION-001
- Other IDs
- IIT-2026-010
- Acronym
- ACTION-001
- Status last verified
- Mar 2026
- First submitted
- 17 Mar 2026
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41125112Llovet 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.
PubMed 33510460Vogel 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.
PubMed 39986353