Advanced Hepatocellular Carcinoma (HCC)Phase 1/2NCT06995105
Personalized Tumor Neoantigen mRNA Therapy for Advanced Hepatocellular Carcinoma
A Phase 1/2 study testing TACE, Sintilimab combined with Bevacizumab and individualized anti-tumor new antigen iNeo-Vac-R01 injection in people with Advanced Hepatocellular Carcinoma (HCC), run by Zhejiang University at 1 site in China.
Trial summary
This study is to evaluate the feasibility and safety of personalized tumor neoantigen mRNA therapy iNeo-Vac-R01 combined with PD-1 monoclonal antibody, anti-VEGFR monoclonal antibody and TACE regimen for the treatment of patients with advanced hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Hepatocellular Carcinoma (HCC)
- What is being tested?
- TACE, Sintilimab combined with Bevacizumab and individualized anti-tumor new antigen iNeo-Vac-R01 injection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 9 Apr 2025to 1 Apr 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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) Subjects who meet all the following inclusion criteria will enter the pre-screening stage of this study and undergo the lesion puncture process:
- Voluntarily sign the informed consent form;
- Aged ≥18 years and ≤75 years, regardless of gender;
- Strictly meet the 2018 American Association for Clinical Diagnosis of Liver Diseases (AASLD) clinical diagnostic criteria for HCC, and imaging assessment is unresectable/metastatic hepatocellular carcinoma (HCC), CNLC stage Ib to IIIb;
- Have not received systemic or local treatment for HCC in the past.
- According to the solid tumor efficacy evaluation criteria (RECIST 1.1), the investigators assess the presence of measurable lesions.
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- Child-Pugh score within 7 points (including 7 points)
- Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1;
- Adequate fresh tumor tissue samples can be obtained for exome and transcriptome sequencing analysis;
- The main organ functions of the heart, liver and kidney are normal:
- QTc (corrected QT interval) in the electrocardiogram: ≤450 milliseconds for men, or ≤470 milliseconds for women;
- Coagulation function: international normalized ratio (INR) ≤1.5×ULN; activated partial thromboplastin time (APTT) ≤1.5 times ULN;
- Hematological indicators: white blood cells ≥3.5×109/L; absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin (HGB) ≥10 g/dL; platelet count (PLT) ≥80×109/L;
- Biochemical indicators: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN (ALT or AST ≤ 5 times ULN is allowed for patients with liver metastasis and liver cancer); serum creatinine and urea nitrogen ≤ 1.5 times ULN;
- Male patients with fertility and female patients of childbearing age agree to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last administration of the trial drug; women of childbearing age include premenopausal women and women within 2 years after menopause;
- Able to follow the study protocol and follow-up process.
- Subjects who meet all the following inclusion criteria will enter the formal screening phase of this study and enter the study medication process:
- Voluntarily sign the informed consent form;
- Aged ≥18 years and ≤75 years, regardless of gender;
- Primary hepatocellular carcinoma confirmed by pathology (histology or cytology);
- Have not received any systemic treatment.
- According to the solid tumor efficacy evaluation criteria (RECIST 1.1), the researcher assesses the presence of measurable lesions.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
- Normal function of the heart, liver and kidney:
- QTc (corrected QT interval) in the electrocardiogram: ≤450 milliseconds for men, or ≤470 milliseconds for women;
- Coagulation function: international normalized ratio (INR) ≤1.5×ULN; activated partial thromboplastin time (APTT) ≤1.5 times ULN;
- Hematological indicators: white blood cells ≥3.5×109/L; absolute neutrophil count (ANC) ≥1.5×109/L; hemoglobin (HGB) ≥10 g/dL; platelet count (PLT) ≥80×109/L;
- Biochemical indicators: serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN (ALT or AST ≤ 5 times ULN is allowed for patients with liver metastasis and liver cancer); serum creatinine and urea nitrogen ≤ 1.5 times ULN;
- Male patients with fertility and female patients of childbearing age agree to take effective contraceptive measures from the signing of the informed consent form to 6 months after the last administration of the trial drug; women of childbearing age include premenopausal women and women within 2 years after menopause;
- Able to follow the study protocol and follow-up process.
Who cannot join
- 1) Diffuse HCC. 2) Known fibrolamellar HCC, cholangiocarcinoma, and mixed HCC. 3) Concomitant tumor thrombus in the main portal vein or contralateral portal vein, superior mesenteric vein, or vena cava.
- 4) History of meningeal disease; presence of central nervous system metastases or meningeal metastases.
- 5) History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, or idiopathic pneumonia, or evidence of active pneumonia on screening chest CT.
- 6) Patients with other malignant tumors at the same time, but basal cell carcinoma, thyroid cancer, cervical atypical hyperplasia, etc. that have been cured, have been in a disease-free state for more than 5 years or are considered by researchers to be less likely to relapse; 7) Patients with a history of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation; 8) Patients with immunosuppressants, that is, those who need to take immunosuppressants regularly 4 weeks before the screening period and during the clinical study, including but not limited to the following: those with severe asthma, autoimmune diseases or immunodeficiency, those who are treated with immunosuppressive drugs, and those with a known history of primary immunodeficiency; but excluding type 1 diabetes, autoimmune-related hypothyroidism requiring hormone treatment, and vitiligo and psoriasis that do not require systemic treatment; 9) Active bacterial or fungal infection confirmed by clinical diagnosis; active tuberculosis or history of tuberculosis; 10) Those with positive human immunodeficiency virus (HIV) antibody test, positive Treponema pallidum (TP) antibody test, active hepatitis C (positive hepatitis C virus (HCV) antibody and HCV RNA result is positive), active hepatitis B; 11) Herpes virus infection (except for those with scabs for more than 4 weeks); respiratory virus infection (except for those who have recovered for more than 4 weeks); 12) Uncontrolled complications include but are not limited to active infection, symptomatic congestive heart failure, unstable angina, arrhythmia; severe coronary artery disease or cerebrovascular disease, or other diseases that the investigators believe are not suitable for inclusion; 13) History of drug abuse, clinical, psychological or social factors that affect informed consent or research implementation; history of mental illness; 14) History of food, drug or vaccine allergy, or other potential immunotherapy allergies considered by the investigator.
- 15) Pregnant or lactating women; 16) Those who the investigators believe are not suitable for inclusion or may not be able to complete this trial for other reasons.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
the First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Yiwen Chen, +8619941463683, yiwenchen0705@126.com
About this study
Official title: Clinical Study to Evaluate the Safety and Efficacy of Personalized Tumor Neoantigen mRNA Therapy Combined With PD-1 Monoclonal Antibody and TACE for Advanced Hepatocellular Carcinoma
This study is to evaluate the feasibility and safety of personalized tumor neoantigen mRNA therapy iNeo-Vac-R01 combined with PD-1 monoclonal antibody, anti-VEGFR monoclonal antibody and TACE regimen for the treatment of patients with advanced hepatocellular carcinoma.
- Conditions
- Advanced Hepatocellular Carcinoma (HCC)
- Being tested
- TACE, Sintilimab combined with Bevacizumab, individualized anti-tumor new antigen iNeo-Vac-R01 injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TACEProcedure or surgery
The first day of TACE treatment is the first day (D1). TACE is started on D1. Subsequent TACE is arranged by the investigator based on a comprehensive assessment of the patient's physical condition, disease progression, adverse reactions, etc. The total number of TACEs shall not exceed 4 times, with at least 4 weeks between each two times.
Sintilimab combined with BevacizumabDrug
Sintilimab (200 mg) combined with bevacizumab (Dayoutong injection, 15 mg/kg), intravenous infusion, once every 3 weeks, until the patient is intolerant or the tumor progresses
individualized anti-tumor new antigen iNeo-Vac-R01 injectionBiological
The individualized anti-tumor new antigen iNeo-Vac-R01 injection was commissioned by Hangzhou Nuanjin Biotechnology Co., Ltd., and all patients were admitted into the therapeutic intervention group. According to the results of previous non-clinical studies, the individualized mRNA injection of 100 μ g was a tolerable dose.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE) | Experimental | 1. After pathological diagnosis, the patient will pass the screening of the inclusion group and enter the study medication process;
2. During the screening period, the patient can start TACE treatment first, and the subsequent treatment will be arranged by the researcher based on the patient's physical condition, disease progression, etc. The total number shall ≤ 4 times, and the interval between each two times shall be at least 4 weeks;
3. After the patient enters the study medication process, he/she needs to first use sintilimab (200 mg) combined with bevacizumab (Dayoutong injection, 15 mg/kg), intravenous infusion, once every 3 weeks, until the patient is intolerant or the tumor progresses; the first use of sintilimab and Dayutong injection is the first day (D1)
4. D43±3 (week 7±3 days), the first efficacy evaluation, if the patient has no disease progression, he/she will receive treatment (sintilimab Q3W + bevacizumab Q3W + the first batch of personalized mRNA inject Q3W) Receives: Procedure: TACE; Drug: Sintilimab combined with Bevacizumab; Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
According to the Commonly Used Adverse Event Criteria (CTCAE version 5.0), the number of subjects with adverse events and/or dose-limiting toxicity was counted as an indicator of the safety and tolerable dose of iNeo-Vac-R01 injection.
Measured: The evaluation period was the dosing observation period and the safety follow-up period (21±3 days after the last dose).
Secondary outcomes (7)
Objective response rate (ORR)
Measured: Up to 2 years
Disease control rate (DCR)
Measured: Up to 2 years
Conversion rate
the proportion of patients with initially inoperable tumors who are successfully converted to patients who can undergo radical surgical resection after systemic treatment in conversion therapy
Measured: Up to 2 years
Progression-free survival （PFS）
Measured: Up to 2 years
Overall survival (OS)
Measured: Up to 2 years
Progression-free survival Rate（1-Y-PFS%, 2-Y-PFS%,3-Y-PFS%）
Measured: Up to 3 years
Overall Survival Rate (1-Y-OS%,2-Y-OS%,3-Y-OS%)
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2025
- Study start9 Apr 2025
- Primary completion1 Apr 2027 (estimated)
- Study completion1 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- More trials run by Zhejiang 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang University
- Sponsor type
- University, hospital or other
- Collaborators
- Hangzhou Neoantigen Therapeutics Co., Ltd.
- Responsible party
- Principal investigator, TingBo Liang, First Affiliated Hospital of Zhejiang University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06995105
- Sponsor's protocol ID
- CISLD-13
- Status last verified
- May 2025
- First submitted
- 9 Apr 2025
- Last updated
- 29 May 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study to Evaluate the Safety and Efficacy of Personalized Tumor Neoantigen mRNA Therapy Combined With PD-1 Monoclonal Antibody and TACE for Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT06995105
- Acronym / sponsor ID
- CISLD-13
- Conditions
- Advanced Hepatocellular Carcinoma (HCC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Zhejiang UniversityUniversity, hospital or other
- Collaborators
- Hangzhou Neoantigen Therapeutics Co., Ltd.
- Study start
- 9 Apr 2025 (actual)
- Primary completion
- 1 Apr 2027 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 29 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to evaluate the feasibility and safety of personalized tumor neoantigen mRNA therapy iNeo-Vac-R01 combined with PD-1 monoclonal antibody, anti-VEGFR monoclonal antibody and TACE regimen for the treatment of patients with advanced hepatocellular carcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE) | Experimental | Procedure: TACE, Drug: Sintilimab combined with Bevacizumab, Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection1. After pathological diagnosis, the patient will pass the screening of the inclusion group and enter the study medication process; 2. During the screening period, the patient can start TACE treatment first, and the subsequent treatment will be arranged by the researcher based on the patient's physical condition, disease progression, etc. The total number shall ≤ 4 times, and the interval between each two times shall be at least 4 weeks; 3. After the patient enters the study medication process, he/she needs to first use sintilimab (200 mg) combined with bevacizumab (Dayoutong injection, 15 mg/kg), intravenous infusion, once every 3 weeks, until the patient is intolerant or the tumor progresses; the first use of sintilimab and Dayutong injection is the first day (D1) 4. D43±3 (week 7±3 days), the first efficacy evaluation, if the patient has no disease progression, he/she will receive treatment (sintilimab Q3W + bevacizumab Q3W + the first batch of personalized mRNA inject Q3W) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- (1) Subjects who meet all the following inclusion criteria will enter the pre-screening stage of this study and undergo the lesion puncture process:
Key exclusion criteria (5 listed)
- 1) Diffuse HCC. 2) Known fibrolamellar HCC, cholangiocarcinoma, and mixed HCC. 3) Concomitant tumor thrombus in the main portal vein or contralateral portal vein, superior mesenteric vein, or vena cava.
- 4) History of meningeal disease; presence of central nervous system metastases or meningeal metastases.
- 5) History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, or idiopathic pneumonia, or evidence of active pneumonia on screening chest CT.
- 6) Patients with other malignant tumors at the same time, but basal cell carcinoma, thyroid cancer, cervical atypical hyperplasia, etc. that have been cured, have been in a disease-free state for more than 5 years or are considered by researchers to be less likely to relapse; 7) Patients with a history of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation; 8) Patients with immunosuppressants, that is, those who need to take immunosuppressants regularly 4 weeks before the screening period and during the clinical study, including but not limited to the following: those with severe asthma, autoimmune diseases or immunodeficiency, those who are treated with immunosuppressive drugs, and those with a known history of primary immunodeficiency; but excluding type 1 diabetes, autoimmune-related hypothyroidism requiring hormone treatment, and vitiligo and psoriasis that do not require systemic treatment; 9) Active bacterial or fungal infection confirmed by clinical diagnosis; active tuberculosis or history of tuberculosis; 10) Those with positive human immunodeficiency virus (HIV) antibody test, positive Treponema pallidum (TP) antibody test, active hepatitis C (positive hepatitis C virus (HCV) antibody and HCV RNA result is positive), active hepatitis B; 11) Herpes virus infection (except for those with scabs for more than 4 weeks); respiratory virus infection (except for those who have recovered for more than 4 weeks); 12) Uncontrolled complications include but are not limited to active infection, symptomatic congestive heart failure, unstable angina, arrhythmia; severe coronary artery disease or cerebrovascular disease, or other diseases that the investigators believe are not suitable for inclusion; 13) History of drug abuse, clinical, psychological or social factors that affect informed consent or research implementation; history of mental illness; 14) History of food, drug or vaccine allergy, or other potential immunotherapy allergies considered by the investigator.
- 15) Pregnant or lactating women; 16) Those who the investigators believe are not suitable for inclusion or may not be able to complete this trial for other reasons.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TACEThe first day of TACE treatment is the first day (D1). TACE is started on D1. Subsequent TACE is arranged by the investigator based on a comprehensive assessment of the patient's physical condition, disease progression, adverse reactions, etc. The total number of TACEs shall not exceed 4 times, with at least 4 weeks between each two times. | Procedure or surgery | Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE) |
| Sintilimab combined with BevacizumabSintilimab (200 mg) combined with bevacizumab (Dayoutong injection, 15 mg/kg), intravenous infusion, once every 3 weeks, until the patient is intolerant or the tumor progresses | Drug | Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE) |
| individualized anti-tumor new antigen iNeo-Vac-R01 injectionThe individualized anti-tumor new antigen iNeo-Vac-R01 injection was commissioned by Hangzhou Nuanjin Biotechnology Co., Ltd., and all patients were admitted into the therapeutic intervention group. According to the results of previous non-clinical studies, the individualized mRNA injection of 100 μ g was a tolerable dose. | Biological | Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE) |
Primary outcome
Adverse events
Time frame: The evaluation period was the dosing observation period and the safety follow-up period (21±3 days after the last dose).
According to the Commonly Used Adverse Event Criteria (CTCAE version 5.0), the number of subjects with adverse events and/or dose-limiting toxicity was counted as an indicator of the safety and tolerable dose of iNeo-Vac-R01 injection.
7 secondary outcomes
Objective response rate (ORR)
Time frame: Up to 2 years
Disease control rate (DCR)
Time frame: Up to 2 years
Conversion rate
Time frame: Up to 2 years
Progression-free survival （PFS）
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
Progression-free survival Rate（1-Y-PFS%, 2-Y-PFS%,3-Y-PFS%）
Time frame: Up to 3 years
Overall Survival Rate (1-Y-OS%,2-Y-OS%,3-Y-OS%)
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TACE, Sintilimab combined with Bevacizumab and individualized anti-tumor new antigen iNeo-Vac-R01 injection in people with Advanced Hepatocellular Carcinoma (HCC), run by Zhejiang University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tingbo Liang (+8619941463683, liangtingbo@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: The evaluation period was the dosing observation period and the safety follow-up period (21±3 days after the last dose).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2025.