Real-World Study of Personalized Neoantigen-pulsed Autologous Dendritic Cell Injections （ZSNeo-DC ）for Malignant Solid Tumors
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
This is a prospective, single-center, open-label, real-world clinical study designed to evaluate the safety, efficacy, and immunogenicity of Personalized neoantigen-pulsed autologous dendritic cell Injections （ZSNeo-DC）in patients with malignant solid tumors. The study protocol received approval from the institutional review board and ethics committee of Beidaihe Hospital, adhering to ethical guidelines. Written informed consent was obtained from all participants in accordance with the principles of the Declaration of Helsinki. Approximately 100 patients will be enrolled in multiple tumor-specific cohorts which will be independently statistically analyzed. ZSNeo-DC will be manufactured by Good Manufacturing Practice (GMP). Participants will receive seven subcutaneous injections of personalized DCs administered on Days 1, 8, 15, 22, 36, 50, and 64, either as monotherapy or in combination with immune checkpoint inhibitors according to routine clinical practice. Tumor response, progression-free survival, overall survival, safety, and antigen-specific immune responses will be evaluated throughout the study.
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
- •Participants must meet all of the following criteria:
- •Male or female participants aged 18 to 75 years, inclusive.
- •Histologically or cytologically confirmed malignant solid tumor.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate hematologic function, including:
- •Adequate hepatic function:
- •Adequate renal function:
- •Adequate coagulation function:
- •Adequate pancreatic function:
- •Availability of sufficient tumor tissue and peripheral blood samples for whole-exome sequencing (WES), RNA sequencing (RNA-seq), and neoantigen identification.
- •Adequate peripheral venous access for peripheral blood mononuclear cell (PBMC) collection by leukapheresis.
- •Left ventricular ejection fraction (LVEF) ≥50%.
- •Estimated life expectancy of at least 3 months.
- •Women of childbearing potential must have a negative pregnancy test within 7 days before the first administration of study treatment.
- •Male participants and women of childbearing potential must agree to use highly effective contraception during treatment and for 3 months after the final administration.
- •Ability to understand and voluntarily sign written informed consent.
- •Willingness and ability to comply with study procedures and scheduled follow-up assessments.
排除标准
- •Participants meeting any of the following criteria will be excluded:
- •T-cell-derived malignant tumors.
- •Previous allogeneic hematopoietic stem cell transplantation or solid organ transplantation.
- •Active autoimmune disease requiring systemic treatment.
- •Active uncontrolled bacterial, viral, fungal, or opportunistic infection.
- •Known human immunodeficiency virus (HIV) infection.
- •Active hepatitis B or hepatitis C infection that is not adequately controlled.
- •Clinically significant cardiovascular disease, including uncontrolled hypertension, unstable angina, myocardial infarction within 6 months, severe arrhythmia, or congestive heart failure.
- •Severe pulmonary, hepatic, renal, neurologic, psychiatric, or other uncontrolled systemic diseases judged by the investigator to interfere with study participation.
- •Pregnant or breastfeeding women.
- •Receipt of systemic immunosuppressive therapy within 14 days before leukapheresis, except physiologic corticosteroid replacement.
- •Receipt of blood transfusion, erythropoietin, granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days before PBMC collection.
- •Inability to undergo leukapheresis.
- •Any condition that, in the investigator's opinion, would place the participant at unacceptable risk or compromise study integrity.
研究组 & 干预措施
Personalized Dendritic Cell Injection
Participants will receive personalized neoantigen-pulsed autologous dendritic cell Injections administered subcutaneously at a fixed dose of 1×10^7 cells per injection on Days 1, 8, 15, 22, 36, 50, and 64. Immune checkpoint inhibitors may be administered concomitantly according to routine clinical practice and investigator judgment.
干预措施: Personalized neoantigen-pulsed autologous dendritic cell Injections （ZSNeo-DC） (Biological)
Personalized Dendritic Cell Injection
Participants will receive personalized neoantigen-pulsed autologous dendritic cell Injections administered subcutaneously at a fixed dose of 1×10^7 cells per injection on Days 1, 8, 15, 22, 36, 50, and 64. Immune checkpoint inhibitors may be administered concomitantly according to routine clinical practice and investigator judgment.
干预措施: Immune Checkpoint Inhibitors (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: From first study treatment until 12 months after treatment initiation
Objective tumor response will be evaluated according to RECIST version 1.1 or other disease-specific response criteria, as applicable.
次要结局
- Overall Survival(From first treatment until death from any cause, assessed up to 24 months.)
- Disease Control Rate(Up to 12 months.)
- Best Overall Response(Up to 12 months.)
- Clinical Benefit Rate(Up to 12 months.)
- Incidence of Adverse Events(From informed consent until 30 days after the last administration of study treatment.)
- Progression-Free Survival(From first study treatment until disease progression or death, assessed up to 24 months)
- Number of Participants With Serious Adverse Events(From informed consent through 30 days after the last administration of personalized dendritic cell injection.)