A Clinical Study on the Safety, Tolerability and Efficacy of Neoantigen-based Personalized mRNA Therapy iNeo-Vac-R01 Plus PD-1 Inhibitor in Adjuvant Treatment of Liver Cancer Post Radical Resection

Inclusion criteria

• Aged 18 to 75 years old (at the time of signing the informed consent form).
• Patients with histopathologically or cytologically confirmed hepatocellular carcinoma (HCC) eligible for radical resection; no tumor thrombus in the portal vein, hepatic vein or bile duct on pre-operative imaging; for multinodular patients, the number of tumor nodules ≤ 3 and no extrahepatic metastasis; clear margins of all tumor nodules and negative surgical margins after radical resection.
• High risk of postoperative recurrence, where high risk is defined as a single tumor lesion with microvascular invasion, or 2-3 tumor lesions; intermediate risk is defined as a single tumor lesion with a diameter > 5 cm and no microvascular invasion.
• Able to complete at least 4 cycles of the standard postoperative adjuvant therapy regimen in accordance with clinical guidelines; and toxicities from prior anti-tumor therapy have recovered to ≤ Grade 1 per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, or to the levels specified in the inclusion/exclusion criteria (Note: Excluding Grade ≤ 2 toxicities such as alopecia, fatigue, or other toxicities assessed by the investigator as having no significant risk).
• Expected survival time of at least 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Sufficient tumor tissue samples can be obtained for genetic analysis: for puncture samples, at least 2 core biopsy tissues with tumor purity ≥ 50%; for surgical samples, a soybean-sized tissue sample.
• Echocardiography assessment: left ventricular ejection fraction (LVEF) ≥ 50%.
• Hematological parameters meeting the following requirements:

① Routine blood test criteria

• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Hemoglobin (Hb) ≥ 90 g/L (no red blood cell transfusion within 7 days before the first administration of the mRNA injectable formulation)
• Platelet count ≥ 80 × 10⁹/L ② Biochemical parameter criteria

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• Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
• Serum albumin ≥ 28 g/L
• Serum creatinine ≤ 1.5 × ULN, or estimated glomerular filtration rate (eGFR) ≥ 50 mL/min (per Cockcroft-Gault formula)
• Coagulation function criteria: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5 × ULN (in patients not receiving anticoagulant therapy)
• For pregnant or lactating women: excluded; for women of childbearing potential, negative serum pregnancy test within 7 days before enrollment, no planned pregnancy in the short term, and willingness to adopt effective contraceptive measures (or other fertility control methods) before enrollment and during the study.
• Male patients are willing to adopt appropriate contraceptive methods.
• Able to comply with the study protocol and follow-up procedures.
• Voluntarily participate in the study and sign the informed consent form. If a subject is unable to read the informed consent form (e.g., illiterate subjects), a witness shall observe the informed consent process and sign the form together with the subject.

Exclusion criteria

• A history of malignancy requiring anti-tumor therapy within 5 years prior to study enrollment (excluding treated Stage I prostate cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, papillary thyroid cancer, and non-melanoma skin cancer).
• Major surgical treatment, significant traumatic injury within 2 weeks before the first personalized immunotherapy administration; or presence of unhealed wounds or fractures for a long time.
• No eligible neoantigens for personalized immunotherapy identified by sequencing data analysis.
• Planned or prior history of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation.
• Requirement for immunosuppressant therapy, systemic or absorbable local hormonal therapy for immunosuppressive purposes, and continued use within 7 days before the first study drug administration (excluding systemic glucocorticoids at a daily dose < 10 mg prednisone equivalent).
• Receipt of any other vaccine within 4 weeks before study treatment initiation; or anticipated need for any other vaccine during the study treatment period or within 60 days after the last study treatment administration.
• Presence of active or uncontrolled severe infection (including fungal, bacterial, viral or other infections); or active tuberculosis.
• Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA titer above the normal range; positive hepatitis C virus (HCV) antibody with peripheral blood hepatitis C virus (HCV) RNA above the normal range; positive human immunodeficiency virus (HIV) antibody; positive syphilis test.
• A history of autoimmune disease or immunodeficiency with immunosuppressant therapy (excluding vitiligo, Type 1 diabetes mellitus, autoimmune hypothyroidism requiring hormonal therapy, and psoriasis not requiring systemic treatment); or a known history of primary immunodeficiency.
• Cardio-cerebrovascular events: a history or current diagnosis of Grade ≥ 3 cardiac valvular disease; or heart failure (New York Heart Association [NYHA] Class ≥ II), myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack (TIA) within 8 weeks before the first mRNA treatment administration; or cardiac-related surgery (including coronary artery bypass grafting [CABG], percutaneous coronary intervention [PCI]) within 8 weeks before the first drug administration; or severe electrocardiogram (ECG) abnormalities (e.g., ventricular flutter, ventricular fibrillation, polymorphic ventricular tachycardia, sick sinus syndrome, third-degree atrioventricular block without pacemaker therapy, QTc interval ≥ 480 ms, and other conditions assessed by the investigator as severely abnormal); or poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg); or other cardio-cerebrovascular diseases assessed by the investigator as unsuitable for study participation.
• Respiratory diseases: a history or current diagnosis of pulmonary fibrosis, interstitial lung disease, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, severe asthma, etc.; or patients with complicated pulmonary arterial hypertension or severe impairment of pulmonary function.
• Clinically significant moderate to severe ascites; uncontrolled or moderate to large pleural effusion or pericardial effusion.
• Substance abuse; or clinical, psychological or social factors that may affect the informed consent process or study implementation.
• A history of hypersensitivity to prior immunotherapeutic agents or vaccines; or other potential hypersensitivity to immunotherapy as assessed by the investigator.
• Assessed by the investigator as unsuitable for enrollment, or unable to complete the study for other reasons.
• Vulnerable populations, including patients with mental illness, cognitive impairment, critically ill patients, pregnant/lactating women, etc.