Personalized Tumor Neoantigen mRNA Therapy for Advanced Hepatocellular Carcinoma

NCT06995105 | Recruiting Phase 1

• 1 other identifier: CISLD-13
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  Up to 2 years

• Disease control rate (DCR)

  Up to 2 years

• Conversion rate

  Up to 2 years

• Progression-free survival （PFS）

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

Study Arms (1)

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)

Procedure: TACE; Drug: Sintilimab combined with Bevacizumab; Biological: individualized anti-tumor new antigen iNeo-Vac-R01 injection

Interventions

TACE PROCEDURE

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.

Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE)

Sintilimab combined with Bevacizumab DRUG

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

Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE)

individualized anti-tumor new antigen iNeo-Vac-R01 injection BIOLOGICAL

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.

Experimental group (mRNA therapy+PD-1+anti-VEGFR+TACE)

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• \) 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.
• \) History of meningeal disease; presence of central nervous system metastases or meningeal metastases.
• \) History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, or idiopathic pneumonia, or evidence of active pneumonia on screening chest CT.

Sponsors & Collaborators

• Zhejiang University: lead
• Hangzhou Neoantigen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

the First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Tingbo Liang

CONTACT

+8619941463683; liangtingbo@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: May 29, 2025
• Study Start: April 9, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 29, 2025

Record last verified: 2025-05

Locations

CN (1)