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

NCT07053072 | Recruiting Phase 1

• 1 other identifier: 2025-755
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Adverse events

  Adverse events defined as the number of participants with adverse events

  One month after the first vaccine dose

Secondary Outcomes (7)

• Disease Control Rate (DCR)

  Two month after the first vaccine dose

• DRR (Durable Response Rate)

  Six month after the first vaccine dose

• DOR (Duration of Response)

  Six month after the first vaccine dose

• TTR (Response Time）

  Six month after the first vaccine dose

• PFS (progression-free survival)

  Six month after the first vaccine dose

Study Arms (2)

Low Dose

EXPERIMENTAL

Low-dose PD-1 mRNA LNP vaccine for advanced primary hepatocellular carcinoma failing standard therapy

Drug: Low Dose PD-1 mRNA LNP Vaccine

High Dose

EXPERIMENTAL

High Dose PD-1 mRNA LNP Vaccine for Advanced Primary Hepatocellular Carcinoma Failing Standard Treatment

Drug: High dose PD-1 mRNA LNP vaccines

Interventions

Low Dose PD-1 mRNA LNP Vaccine DRUG

Patients will receive PD-1 mRNA LNP vaccine at 50 mcg weekly for the first 4 doses and a 5th dose 1 month after the 4th dose.

Also known as: PD-1 mRNA LNP vaccine at 50 mcg

Low Dose

High dose PD-1 mRNA LNP vaccines DRUG

Patients will receive PD-1 mRNA LNP vaccine at 100 mcg weekly for the first 4 doses and a 5th dose 1 month after the 4th dose.

Also known as: PD-1 mRNA LNP vaccine at 100 mcg

High Dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients: ≥18 years of age; ≤70 years of age;
• Recurrent or metastatic hepatocellular carcinoma that has failed second-line standard therapy.
• 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);
• ECOG physical condition score: 0 to 1;
• Expected survival ≥ 3 months;
• 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%.
• Good compliance and family agreement to cooperate in receiving survival follow-up.

You may not qualify if:

• Participation in a clinical trial of another drug within 4 weeks;
• 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);
• 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.
• For female subjects: women who are pregnant or breastfeeding.
• Patients with active tuberculosis, bacterial or fungal infection (≥ grade 2 of NCI-CTCAE 5.0); HIV infection; active HBV infection; HCV infection.
• Those with a history of psychotropic substance abuse that they are unable to abstain from or those with mental disorders;
• 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).
• Patients who have been inoculated with mRNA drugs.
• Participation in clinical trials involving lipid nanoparticles, a component of the study vaccine.
• Contraindications to intramuscular injection.
• History of substance abuse or known medical, psychological or social conditions such as alcohol or drug abuse.
• 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).
• 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.
• 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.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (2)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

Sichuan University West China Hospital

Chengdu, Sichuan, China

RECRUITING

Related Publications (13)

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• Wu Y, Li W, Chen X, Wang H, Su S, Xu Y, Deng X, Yang T, Wei M, Li L, Liu Y, Yang J, Li W. DOG1 as a novel antibody-drug conjugate target for the treatment of multiple gastrointestinal tumors and liver metastasis. Front Immunol. 2023 Jan 26;14:1051506. doi: 10.3389/fimmu.2023.1051506. eCollection 2023.

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• Sabnis S, Kumarasinghe ES, Salerno T, Mihai C, Ketova T, Senn JJ, Lynn A, Bulychev A, McFadyen I, Chan J, Almarsson O, Stanton MG, Benenato KE. A Novel Amino Lipid Series for mRNA Delivery: Improved Endosomal Escape and Sustained Pharmacology and Safety in Non-human Primates. Mol Ther. 2018 Jun 6;26(6):1509-1519. doi: 10.1016/j.ymthe.2018.03.010. Epub 2018 Mar 14.

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• Selvaggio G, Leonardelli L, Lofano G, Fresnay S, Parolo S, Medini D, Siena E, Marchetti L. A quantitative systems pharmacology approach to support mRNA vaccine development and optimization. CPT Pharmacometrics Syst Pharmacol. 2021 Dec;10(12):1448-1451. doi: 10.1002/psp4.12721. Epub 2021 Oct 21. No abstract available.

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• Xu S, Yang K, Li R, Zhang L. mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection. Int J Mol Sci. 2020 Sep 9;21(18):6582. doi: 10.3390/ijms21186582.

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• Linares-Fernandez S, Lacroix C, Exposito JY, Verrier B. Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response. Trends Mol Med. 2020 Mar;26(3):311-323. doi: 10.1016/j.molmed.2019.10.002. Epub 2019 Nov 5.

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• Verbeke R, Hogan MJ, Lore K, Pardi N. Innate immune mechanisms of mRNA vaccines. Immunity. 2022 Nov 8;55(11):1993-2005. doi: 10.1016/j.immuni.2022.10.014.

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• Lim SA, Cox A, Tung M, Chung EJ. Clinical progress of nanomedicine-based RNA therapies. Bioact Mater. 2021 Oct 22;12:203-213. doi: 10.1016/j.bioactmat.2021.10.018. eCollection 2022 Jun.

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• Sebastian M, Schroder A, Scheel B, Hong HS, Muth A, von Boehmer L, Zippelius A, Mayer F, Reck M, Atanackovic D, Thomas M, Schneller F, Stohlmacher J, Bernhard H, Groschel A, Lander T, Probst J, Strack T, Wiegand V, Gnad-Vogt U, Kallen KJ, Hoerr I, von der Muelbe F, Fotin-Mleczek M, Knuth A, Koch SD. A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. Cancer Immunol Immunother. 2019 May;68(5):799-812. doi: 10.1007/s00262-019-02315-x. Epub 2019 Feb 15.

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MeSH Terms

Conditions

Liver Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• Xingchen Peng

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xingchen Peng

CONTACT

18980606753; pxx2014@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD，professor

Model Details: This single-centre, open-label, single-arm trial uses a dose-escalation framework to evaluate the safety and biological activity of PD-1 mRNA LNP in the treatment of patients with advanced hepatocellular carcinoma who have failed standard therapy. All participants will maintain a fixed chemotherapy/immunotherapy regimen based on their respective malignancies, with only the dose of PD-1 mRNA LNP changing. Three cases will be enrolled in each dose group, with the planned dose groups being the 50 μg, 75 μg and 100 μg groups. It consisted of 5 doses of basal immunisation and subsequent personalised treatment. For the base immunisation, the first 4 doses were administered 1 week apart each and the 5th dose was administered 1 month after the 4th dose. Dose-limiting toxicity (DLT) will be monitored through a 21-day monitoring window. Escalation decisions will be made using a Bayesian Optimal Interval (BOIN) approach, with DLT classification following the

Study Record Dates

• First Submitted: June 30, 2025
• First Posted: July 8, 2025
• Study Start: October 23, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: April 23, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)