PD-1 mRNA lipid‑nanoparticle vaccine for advanced liver cancer

A Prospective，Single Arm Clinicial Trial Evaluating PD-1 mRNA LNP Vaccine for the Treatment of Advanced Primary Hepatocellular Carcinoma Failing Standard Therapy

This trial will try a PD‑1 mRNA vaccine delivered in lipid nanoparticles as a treatment for adults with advanced hepatocellular carcinoma who have not responded to standard therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Locations: 2 sites (Chengdu, Sichuan and 1 other locations)
• Trial ID: NCT07053072 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 dose‑finding trial of a PD‑1 mRNA vaccine formulated in lipid nanoparticles in adults with recurrent or metastatic hepatocellular carcinoma after failure of second‑line therapy. Participants receive either a low or high dose of the PD‑1 mRNA LNP vaccine and are monitored for safety, tolerability, immune responses, and early signs of tumor shrinkage per RECIST. Key enrollment requirements include measurable disease, ECOG 0–1, adequate organ function, and expected survival of at least three months. The trial is conducted at West China Hospital, Sichuan University, with serial clinical, laboratory, and imaging assessments to characterize adverse events and preliminary efficacy.

Who should consider this trial

Good fit: Adults aged 18–70 with recurrent or metastatic hepatocellular carcinoma that failed second‑line standard therapy, a measurable lesion by RECIST, ECOG 0–1, and adequate blood and organ function are the intended candidates.

Not a fit: Patients outside the 18–70 age range, those with poor performance status (ECOG >1), severe organ dysfunction, no measurable disease, or earlier‑stage disease are unlikely to benefit from this Phase 1 investigational vaccine.

Why it matters

Potential benefit: If successful, the vaccine could stimulate anti‑tumor immune responses and provide a new treatment option for people with advanced liver cancer who have exhausted standard therapies.

How similar studies have performed: Early‑phase mRNA cancer vaccines have shown the ability to provoke immune responses in some cancers, but meaningful clinical benefit has been limited to date and PD‑1–targeted mRNA therapy remains largely novel.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients: ≥18 years of age; ≤70 years of age;
2. Recurrent or metastatic hepatocellular carcinoma that has failed second-line standard therapy.
3. Patients with at least one target lesion with a measurable diameter according to the RECIST criteria (CT scan of tumor lesions with a long diameter of ≥10mm, CT scan of lymph node lesions with a short diameter of ≥10mm and a layer thickness of no more than 5mm);
4. ECOG physical condition score: 0 to 1;
5. Expected survival ≥ 3 months;
6. Good function of major organs, i.e., relevant examination indexes within 14 days prior to randomization meet the following requirements:

   * Routine blood tests: hemoglobin ≥80g/L (no blood transfusion within 14 days); neutrophil count \>1.5×109 /L; platelet count ≥80×109 /L;
   * Biochemical tests: total bilirubin ≤1.5 × ULN (upper limit of normal); blood alanine aminotransferase (ALT) or blood alanine transaminase (AST) ≤ 2.5 × ULN; if liver metastases, ALT or AST ≤ 5 × ULN; endogenous creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula);
   * cardiac Doppler ultrasound: left ventricular ejection fraction (LVEF) (LVEF) ≥50%.
7. Good compliance and family agreement to cooperate in receiving survival follow-up.

Exclusion Criteria:

1. Participation in a clinical trial of another drug within 4 weeks;
2. Patients with a prior history of other neoplasms, unless cervical cancer in situ, treated squamous skin cancer or epithelial tumor of the bladder or other malignancies that have undergone radical therapy (at least 5 years prior to enrollment);
3. Patients with uncontrolled cardiac clinical symptoms or disease, such as NYHA class 2 or higher heart failure, unstable angina pectoris , myocardial infarction within 1 year, clinically significant Supraventricular or ventricular arrhythmias requiring treatment or intervention.
4. For female subjects: women who are pregnant or breastfeeding.
5. Patients with active tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTCAE 5.0); HIV infection; active HBV infection; HCV infection.
6. Those with a history of psychotropic substance abuse that they are unable to abstain from or those with mental disorders;
7. Subjects with any active autoimmune disease or history of autoimmune disease (e.g., the following, but not limited to : uveitis, enteritis, pituitary gland inflammation, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma that has resolved completely in childhood and does not require any intervention in adulthood may be enrolled; subjects with asthma requiring medical intervention with bronchodilators may not be enrolled).
8. Patients who have been inoculated with mRNA drugs.
9. Participation in clinical trials involving lipid nanoparticles, a component of the study vaccine.
10. Contraindications to intramuscular injection.
11. History of substance abuse or known medical, psychological or social conditions such as alcohol or drug abuse.
12. Known allergy, hypersensitivity or intolerance to the investigational vaccine (including any excipients). Previous history of severe allergy to any drug, food, or vaccination, such as anaphylaxis, allergic laryngeal edema, allergic dyspnea, anaphylactic purpura, thrombocytopenic purpura, localized anaphylactic necrotic reaction (Arthus reaction).
13. The female subject is planning to become pregnant or the male subject's partner is planning to become pregnant during the Screening Period and up to 12 months after the full course of drug administration.
14. In the judgment of the investigator, there is a serious concomitant disease that jeopardizes the patient's safety or interferes with the patient's ability to complete the study.

Where this trial is running

Chengdu, Sichuan and 1 other locations

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• Sichuan University West China Hospital — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Xingchen Peng — West China Hospital
• Study coordinator: Xingchen Peng

Conditions Liver Cancer