Hepatocellular carcinoma
Conditions
Interventions
Cohort 1 (Dose Escalation Phase):mRNA vaccine 200 µg, intramuscular injection
Cohort 2 (Dose Escalation Phase):mRNA vaccine 400 µg, intramuscular injection
Cohort 3 (Dose Escalation Phase):mRNA vaccine 600 µg, intramuscular injection
Cohort 4 (Dose Escalation Phase):mRNA vaccine 800 µg, intramuscular injection
Efficacy Expansion Phase: RP2D Dose mRNA Vaccine Combined with Standard Second-Line Therapy Group:RP2D dose mRNA vaccine combined with standard second-line therapy
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Informed Consent: Voluntarily sign a written informed consent form with good compliance. 2. Age/Gender: Aged 18-75 years, regardless of gender. 3. Diagnosis: Hepatocellular carcinoma (HCC) confirmed by histology/cytology or clinical criteria (CNLC). 4. Prior Treatment Failure: Previously received at least one first-line systemic therapy containing a PD-1/PD-L1 inhibitor or targeted agent (TKI/anti-VEGF), with disease progression (PD) confirmed by imaging (CT/MRI) based on RECIST 1.1 or iRECIST. 5. HLA Typing Match: The subject’s HLA typing includes vaccine-covered subtypes (e.g., HLA-A*02:01 or HLA-A*11:01) to ensure neoantigen presentation potential. 6. Performance Status: ECOG score 0-1. Liver function: Child-Pugh class A, with no history of overt hepatic encephalopathy. 7. At least one measurable lesion according to RECIST 1.1. 8. Life expectancy >=3 months; voluntary signing of the ICF.
Exclusion criteria
Exclusion criteria: 1. Medical History: Presence of other malignancies within the past 5 years; prior treatment with other tumor vaccines; history of organ transplantation (including liver transplantation) or allogeneic hematopoietic stem cell transplantation. 2. Immunity and Allergies: Known severe allergy to mRNA vaccine components (such as PEG, lipids). 3. Active Autoimmune Diseases: Autoimmune diseases requiring systemic treatment (such as corticosteroids, immunosuppressants), e.g., systemic lupus erythematosus, rheumatoid arthritis, etc. Patients with well-controlled hypothyroidism, type 1 diabetes, or vitiligo are allowed to enroll. 4. Infection Status: Active infection requiring intravenous antibiotic treatment. 5. HBV/HCV: Patients with HBV DNA >=2000 IU/mL must receive antiviral therapy and remain stable for more than 2 weeks before enrollment; HCV RNA-positive patients must have completed antiviral therapy or be in a stable phase; patients with HBV/HCV coinfection where both viruses are in an active replication phase are excluded. 6. Comorbidities: Myocardial infarction, unstable angina, or cerebrovascular accident within the past 6 months; severe uncontrolled hypertension; clinically significant ascites (requiring frequent paracentesis); history of gastrointestinal bleeding within the past 6 months or clearly high-risk varices (confirmed by gastroscopy). 7. Medications: Use of systemic corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressants within 14 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-Free Survival;Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease Control Rate;Percentage Change in Tumor Volume Post-Treatment (TGR);Overall Survival; | — |
Countries
China
Contacts
Public ContactGao Qiang
Zhongshan Hospital, Fudan University
Outcome results
None listed