Clinical Trial on the Safety and Efficacy of Neoantigen Antigen mRNA Tumor Vaccine in the Treatment of Advanced Esophageal Cancer and Non-small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
研究概览
简要总结
A single arm, open-label pilot study is designed to determine the safety, tolerability and effectiveness of personalized mRNA tumor vaccine encoding neoantigen in Patients with advanced esophageal cancer and non-small cell lung cancer
详细描述
Primary objectives:
Assessing the safety and tolerability of mRNA personalized tumor vaccines encoding neoantigen for unresectable or metastatic advanced esophageal and non-small cell lung cancers with standard treatment failure or no standard treatment.
Secondary objectives:
Preliminary observation of the efficacy of mRNA personalized tumor vaccines encoding neoantigen for unsurgically resected or metastatic advanced esophageal and non-small cell lung cancers with standard treatment failure or no standard treatment.
Time of tumor progression (TTP); Disease Control Rate (DCR); Objective Remission Rate (ORR); Overall Survival (OS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 18 and 75 (including both ends), with no gender limit;
- •The primary lesion was confirmed by histopathology or cytology as esophageal carcinoma (ⅢC (T4bNanyM0, TanyN3M0), and stage Ⅳ) or non-small cell lung cancer (stage ⅢB-Ⅳ).
- •Patients who have metastatic or locally advanced tumor but failed instandard treatments or not suitable for standard treatments;
- •According to RECIST (V1.1), the efficacy evaluation criteria for solid tumors, there is at least one measurable lesion.
- •Participants with Performance Scale (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) PS
- •Participants must have at least 1 lesion amenable to the mandatory fresh tumor biopsy at study entry
- •Fertile patients must agree to use a reliable contraceptive methods (hormonal or barrier methods or abstinence) during the trial and for at least 12 weeks after the last treatment;
- •The subject voluntarily participates and signs ICF (Informed consent forms).
排除标准
- •Any clinical research drugs, anti-cancer monoclonal antibodies, anti-cancer therapeutic vaccines, immunostimulants (such as IL-2) or using previous investigational drugs within 7 days of the first treatment with mRNA-personalized tumor vaccine or carrelizumab.
- •Patients who have allergies or previous history of biological drug allergy;
- •Patients who are in pregnant or breast-feeding;
- •Patients who are expected to survive less than 3 months during the screening period;
- •Tumor mutation load (TMB) is less than 2.0/Mb or tumor neogenic antigen load (TNB) is less than 0.5/Mb or the number of predicted neoantigen is less than 3;
- •Patients who underwent major surgery or suffered significant trauma within 4 weeks prior to the enrollment (blood collection), or who are expected to undergo major surgery during the study period;
- •Patients with symptoms of brain metastases (Patients with stable brain metastases can be included)
- •Extensive lung metastases from tumors, causing breathing difficulties;
- •Patients who have tumors close to large blood vessels or nerves;
- •A history of severe cardiovascular and cerebrovascular diseases, including but not limited to ventricular arrhythmia requiring clinical intervention; Acute coronary syndrome, myocardial infarction, congestive heart failure, stroke or other grade III and above cardiovascular events within 6 months; New York Heart Association (NYHA) cardiac function grade≥Grade II or left ventricular ejection fraction (LVEF) <50%; Poorly controlled hypertension after standard treatment (systolic blood pressure> 150 mmHg and diastolic blood pressure> 90 mmHg);
- •Patients with active ulcers and gastrointestinal bleeding;
- •Patients with clinically confirmed autoimmune disease have received systemic treatment in the past 2 years; HIV, HCV positive; HBV-DNA≥1×103 copies/mL (or 2×102 IU/mL); Acute EBV or CMV virus infection;
- •Patients with previous history of non-infectious pneumonia requiring steroid therapy or acute lung cancer;
- •Participants with a history of interstitial lung disease;
- •Patients who have a history of organ transplantation or are waiting for organ transplantation;
- •Have any uncontrolled active infection;
- •Immunosuppressed subjects, including those with known immunodeficiency; those who are currently using steroids systemically (except those who are using inhaled steroids recently or currently);
- •Skin diseases (such as psoriasis) may prevent intradermal vaccines from reaching the target area;
- •Who have received chemotherapy, biotherapy, radiotherapy, endocrine therapy, targeted therapy and other tumor treatments, or other experimental drug treatments, or surgery (excluding diagnostic biopsy) within 7 days prior to the first administration of mRNA tumor vaccine treatment;
- •Adverse effects from previous antitumor therapy have not recovered referred to CTCAE (V5.0) rating ≤1 (except hair loss);
- •The investigator evaluates that the subject is unable or unwilling to comply with the requirements of study protocol.
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
时间窗: 24 weeks
During the trial conduction, especially within the 24 weeks of treatment phase when mRNA tumor Vaccine administered, all adverse events (including laboratory abnormality and clinical events) will be closely monitored, and all ≥ grade 3 adverse events per CTCAE will be recorded, including but not limited to the toxicities potentially suspected to relate to injection procedures and/or mRNA Tumor Vaccine therapy as listed below: Fever Chills Nausea, vomiting and other gastrointestinal symptoms Fatigue Hypotension Respiratory distress Tumor lysis syndrome Neutropenia, thrombocytopenia Liver and kidney dysfunction Neutropenia, thrombocytopenia Liver and kidney dysfunction
次要结局
- Time to Tumor Progression (TTP)(2 years)
- Overall Survival (OS)(3 years)
- Disease Control Rate (DCR)(1.5 years)
- Progression-free Survival (PFS)(2 years)