NCT07053072招募中1 期
A Prospective，Single Arm Clinicial Trial Evaluating PD-1 mRNA LNP Vaccine for the Treatment of Advanced Primary Hepatocellular Carcinoma Failing Standard Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Evaluating the Safety and Efficacy of PD-1 mRNA LNP Vaccine Therapy in Patients with Primary Hepatocellular Carcinoma Who Have Failed Advanced Standard Therapy
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Low Dose
Experimental
Low-dose PD-1 mRNA LNP vaccine for advanced primary hepatocellular carcinoma failing standard therapy
干预措施: Low Dose PD-1 mRNA LNP Vaccine (Drug)
High Dose
Experimental
High Dose PD-1 mRNA LNP Vaccine for Advanced Primary Hepatocellular Carcinoma Failing Standard Treatment
干预措施: High dose PD-1 mRNA LNP vaccines (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 2 years
The ratio of participants assessed with complete response (CR) or partial response(PR) as a best overall response.
Adverse events
时间窗: One month after the first vaccine dose
Adverse events defined as the number of participants with adverse events
次要结局
- Disease Control Rate (DCR)(2 years)
- DRR (Durable Response Rate)(2 years)
- DOR (Duration of Response)(2 years)
- TTR (Response Time）(2 years)
- PFS (progression-free survival)(2 years)
- OS (Overall Survival)(2 years)
- TTP (Time to Progression)(2 years)
- 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)
- OS (Overall Survival)(Six month after the first vaccine dose)
- TTP (Time to Progression)(up to 6 months)
研究者
Xingchen Peng
PhD，professor
West China Hospital
研究点 (2)
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