A Clinical Study Evaluating the Safety, Tolerability and Efficacy of the Neoantigen-based Personalized mRNA Therapeutic Technology iNeo-Vac-R01 in Combination With a PD-1 Immune Checkpoint Inhibitor for Adjuvant Therapy After Radical Resection of Liver Cancer
iNeo-Vac-R01, a personalized neoantigen-based mRNA therapeutic technology for tumors, is a customized neoantigen mRNA injectable formulation developed by collecting patients' tumor tissues and peripheral blood, screening appropriate neoantigens via high-throughput sequencing, and encapsulating these neoantigens into mRNA liposomes. It can precisely induce the proliferation of patient-specific T cells to eliminate tumor cells. This tumor therapeutic approach that harnesses the body's own immune system features high efficacy and low toxicity, with milder treatment responses and no severe adverse reactions for patients. This study aims to provide a novel personalized therapeutic strategy for the adjuvant treatment of post-operative liver cancer patients, with the research objectives of prolonging their disease-free survival (DFS) and overall survival (OS) following surgery.
• 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.