YMN-A02 for Advanced Primary Hepatocellular Carcinoma.

Inclusion Criteria:

1. Informed consent: Signed informed consent form approved by the ethics committee.
2. Age and performance status: Aged 18-70 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
3. Patients with histologically confirmed advanced primary hepatocellular carcinoma that has progressed after treatment with anti-angiogenic targeted therapy and immune checkpoint inhibitors.
4. At least one target lesion with a measurable diameter according to RECIST criteria (longest diameter of tumor lesion ≥10 mm on CT scan; short diameter of lymph node lesion ≥10 mm on CT scan; slice thickness ≤5 mm).
5. Life expectancy: ≥3 months.

6. Adequate major organ function, as verified by the following laboratory and test results obtained within 14 days prior to randomization:

   Hematology: Hemoglobin ≥80 g/L (no blood transfusion within 14 days); absolute neutrophil count >1.5×10⁹/L; platelet count ≥80×10⁹/L.

   Biochemistry: Total bilirubin ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; if liver metastases are present, ALT or AST ≤5×ULN; endogenous creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).

   Cardiac assessment: Left ventricular ejection fraction (LVEF) ≥50% as assessed by Doppler echocardiography.

7. Good compliance and follow-up agreement: The patient is compliant and the family agrees to cooperate with survival follow-up.

Exclusion Criteria:

1. Participation in another clinical trial of an investigational drug within 4 weeks prior to enrollment.
2. Previous or concurrent diagnosis of another malignancy, except for the following: carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, urothelial carcinoma of the bladder that has been treated with curative intent, or any other malignancy that has been treated with curative intent with no evidence of recurrence for 5 years or more.
3. Presence of poorly controlled cardiac disease or clinical symptoms, including but not limited to: New York Heart Association (NYHA) Class ≥2 heart failure, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
4. Pregnant or breastfeeding women.
5. Presence of active infection, including but not limited to: active tuberculosis, bacterial or fungal infection requiring systemic treatment (NCI-CTCAE v5.0 Grade ≥2), human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection (HBV DNA above the upper limit of normal), or active hepatitis C virus (HCV) infection (HCV RNA above the upper limit of normal).
6. History of psychotropic substance abuse that cannot be abstained from, or history of mental disorders.
7. Presence of active autoimmune disease or history of autoimmune disease (including but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, etc.). The following are exceptions: vitiligo controlled with topical medication only; childhood asthma that has completely resolved and requires no intervention in adulthood; patients with asthma requiring bronchodilators for medical intervention are not eligible.
8. Prior vaccination with any mRNA-based drug or mRNA formulation.
9. Prior participation in clinical trials involving lipid nanoparticle (LNP) formulations.
10. Contraindications to intravenous infusion.
11. History of drug abuse, or medical, psychological, or social conditions (such as history of alcoholism or drug addiction) that, in the investigator's judgment, may affect compliance with the study.
12. Known allergy, hypersensitivity, or intolerance to any component of the study formulation (including active ingredients and excipients); history of severe drug, food, or vaccine allergy, including but not limited to: anaphylactic shock, allergic laryngeal edema, allergic dyspnea, anaphylactoid purpura, thrombocytopenic purpura, or Arthus reaction.
13. Pregnancy plan (for female subjects or partners of male subjects) from the screening period until 12 months after the last dose.
14. Any concomitant disease that, in the investigator's judgment, may jeopardize patient safety or interfere with the completion of the study.