Personalized neoantigen mRNA vaccine plus PD-1 blocker after liver cancer surgery

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

This will test whether a personalized neoantigen mRNA vaccine called iNeo-Vac-R01 given with a PD-1 inhibitor can help adults at high risk of hepatocellular carcinoma coming back after radical surgery.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sir Run Run Shaw Hospital (Academic / other)
• Drugs / interventions: immunotherapy, radiation, prednisone
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07495215 on ClinicalTrials.gov

What this trial studies

This phase 1–2 program gives patients a personalized mRNA vaccine made from their own tumor and blood sequencing combined with a PD-1 inhibitor as adjuvant therapy after complete surgical removal of hepatocellular carcinoma. Tumor-specific neoantigens are identified by high-throughput sequencing, encoded into mRNA, and delivered in lipid nanoparticles to stimulate patient-specific T cells. The trial will first examine safety and tolerability and then look for signals that the combination prolongs disease-free survival and overall survival. Eligible participants are adults 18–75 at high risk of recurrence (e.g., microvascular invasion or 2–3 nodules) with negative surgical margins and no macrovascular invasion or extrahepatic spread, and treatment is being conducted at Sir Run Run Shaw Hospital in Hangzhou.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed HCC who had radical resection with negative margins, are judged high risk for recurrence (microvascular invasion or 2–3 nodules), and can complete at least four cycles of standard postoperative adjuvant therapy.

Not a fit: Patients with extrahepatic metastasis, macrovascular (portal/hepatic vein/bile duct) tumor thrombus, more than three tumor nodules, positive surgical margins, or who cannot tolerate/complete adjuvant therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could reduce recurrence after surgery and extend disease-free and overall survival for high-risk HCC patients.

How similar studies have performed: Early-phase neoantigen vaccine studies in other cancers have generated tumor-directed immune responses and some clinical signals, and combining neoantigen vaccines with PD-1 blockers has shown promise, but robust efficacy specifically in HCC remains unproven.

Eligibility criteria

Inclusion Criteria:

1. Aged 18 to 75 years old (at the time of signing the informed consent form).
2. 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.
3. 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.
4. 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).
5. Expected survival time of at least 6 months.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
7. 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.
8. Echocardiography assessment: left ventricular ejection fraction (LVEF) ≥ 50%.
9. Hematological parameters meeting the following requirements:

   ① Routine blood test criteria
   1. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
   2. Hemoglobin (Hb) ≥ 90 g/L (no red blood cell transfusion within 7 days before the first administration of the mRNA injectable formulation)
   3. Platelet count ≥ 80 × 10⁹/L ② Biochemical parameter criteria

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   1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
   3. Serum albumin ≥ 28 g/L
   4. Serum creatinine ≤ 1.5 × ULN, or estimated glomerular filtration rate (eGFR) ≥ 50 mL/min (per Cockcroft-Gault formula)
   5. Coagulation function criteria: Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR) ≤ 1.5 × ULN (in patients not receiving anticoagulant therapy)
10. 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.
11. Male patients are willing to adopt appropriate contraceptive methods.
12. Able to comply with the study protocol and follow-up procedures.
13. 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:

1. 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).
2. 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.
3. No eligible neoantigens for personalized immunotherapy identified by sequencing data analysis.
4. Planned or prior history of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation.
5. 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).
6. 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.
7. Presence of active or uncontrolled severe infection (including fungal, bacterial, viral or other infections); or active tuberculosis.
8. 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.
9. 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.
10. 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.
11. 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.
12. Clinically significant moderate to severe ascites; uncontrolled or moderate to large pleural effusion or pericardial effusion.
13. Substance abuse; or clinical, psychological or social factors that may affect the informed consent process or study implementation.
14. A history of hypersensitivity to prior immunotherapeutic agents or vaccines; or other potential hypersensitivity to immunotherapy as assessed by the investigator.
15. Assessed by the investigator as unsuitable for enrollment, or unable to complete the study for other reasons.
16. Vulnerable populations, including patients with mental illness, cognitive impairment, critically ill patients, pregnant/lactating women, etc.

Where this trial is running

Hangzhou, Zhejiang

• Department of General Surgery, Institute of Minimally Invasive Surgery, Sir Run Run Shaw Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yinghua Xu

Conditions Hepatocellular Carcinoma