PD-1 mRNA LNP Vaccine for Advanced Primary Hepatocellular Carcinoma.

Not Applicable

Not yet recruiting

• Conditions: PD-1 mRNA LNP Vaccine; Primary Liver Cancer
• Interventions: Drug: Low Dose PD-1 mRNA LNP Vaccine; Drug: Medium dose PD-1 mRNA LNP vaccines; Drug: High dose PD-1 mRNA LNP vaccines

• Registration Number: NCT07053072
• Lead Sponsor: West China Hospital

Brief Summary

Evaluating the Safety and Efficacy of PD-1 mRNA LNP Vaccine Therapy in Patients with Primary Hepatocellular Carcinoma Who Have Failed Advanced Standard Therapy

Detailed Description

PD-1 mRNA LNP is an immune checkpoint mRNA vaccine loaded with the gene coding for the PD-1 protein Safety, tolerability, immunogenicity and preliminary efficacy of mRNA vaccines with PD-1 as the immunogen in the treatment of primary liver cancer. The aim of this study is to establish a novel PD-1-based mRNA for the treatment of advanced cancers.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-30
• Study First Submitted QC: 2025-06-30
• Last Update Submitted: 2025-06-30
• Study First Posted: 2025-07-08
• Last Update Posted: 2025-07-08
• Study Start: 2025-07-15
• Primary Completion: 2025-07-30
• Study Completion: 2026-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Low Dose	Low Dose PD-1 mRNA LNP Vaccine	Low-dose PD-1 mRNA LNP vaccine for advanced primary hepatocellular carcinoma failing standard therapy
Medium Dose	Medium dose PD-1 mRNA LNP vaccines	Medium Dose PD-1 mRNA LNP Vaccine for Advanced Primary Hepatocellular Carcinoma Failing Standard Treatment
High Dose	High dose PD-1 mRNA LNP vaccines	High Dose PD-1 mRNA LNP Vaccine for Advanced Primary Hepatocellular Carcinoma Failing Standard Treatment

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	2 years	The ratio of participants assessed with complete response (CR) or partial response(PR) as a best overall response.

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate (DCR)	2 years	The ratio of subjects assessed with CR or PR or stable disease (SD) as a best overalresponse.
DRR (Durable Response Rate)	2 years	DRR is defined as the proportion of objective response (CR and PR as determined by the investigator) lasting at least 6 months at any time within 12 months of initiation of treatment.
DOR (Duration of Response)	2 years	DOR is defined as the time from the date when the PR is first recorded or better to the date when the disease progression is first recorded (for the responder, i.e., PR or better). Responders who did not record disease progress will be censored on the date that the last assessment was SD or better.
TTR (Response Time）	2 years	TTR is defined as the time from the date of the first administration to the date of the first record of the objective tumor response (CR and PR determined by the investigator).
PFS (progression-free survival)	2 years	PFS is defined as the duration until disease progression or death in participants fromthe first dose of immunization.
OS (Overall Survival)	2 years	0S is defined as the duration until death in participants from the first dose ofimmunization.
TTP (Time to Progression)	2 years	TTP is defined as the time from the date of first dose to the date of first documented disease progression, as defined by standard disease criteria.

Trial Locations

Locations (1)

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China