A Phase I Study on the Safety and the Efficacy of Personalized Neoantigen-primed Dendritic Cell Vaccines for Refractory Lung Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety]
研究概览
简要总结
Various of immunotherapies are now widely applied in the treatment of lung cancer. Neoantigens arising from the mutations of the tumor genome expressed specifically on the tumor cell instead of normal cells, suggesting that vaccines targeting neoantigens should generate a highly tumor-specific response with minimal off-target effects. Neoantigens are highly suitable for the development of cancer vaccines. The study aims to evaluate the safety and efficacy of neoantigen-loaded dendritic cell (DC) vaccines for refractory lung cancer.
详细描述
Cancer genome research has exploded benefits from the application of modern high-throughput genome sequencing in the past few years. Since usually there are no common antigens expressed on the surfaces of different kinds of tumors, neoantigens which expressed specifically in the individual tumor are chosen to establish tumor-specific vaccines.
30 patients with refractory lung cancer would be enrolled and undergo tumor resection if all requirements are met. The whole-exome sequencing and the bioinformatic analysis of the resected specimens would be performed to identify the neoantigens. Then, candidate neoantigens would be synthesized to pulse the matured DC cells. Neoantigen-primed DC vaccines are provided to the corresponding patients. Each patient would be vaccinated 6 times in total, one shot per week.
Patients enrolled would undergo the schemed follow-up, one time per three months. The side effects, overall survival, and progress-free survival would be recorded. At the end of the research, the safety and efficacy of neoantigen DC vaccines for refractory lung cancer would be evaluated.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years ≤ 70 years at the time of informed consent
- •Signed informed consent to be provided
- •pathologically confirmed lung cancer
- •failed in previous standard chemotherapy and targeted therapy
- •Life expectancy not less than 90 days
- •Karnofsky performance status 0-1
- •adequate organ functions
排除标准
- •Actively infectious condition including hepatitis
- •Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- •Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- •Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- •Active systemic infections, coagulation disorders or any other active major medical illnesses.
- •Patients who are receiving any other investigational agents.
研究组 & 干预措施
Vaccinated group
Neoantigen loaded-DC vaccination will be performed with 6 doses in total, once per week, adjacent lymph-node injection.
干预措施: Neoantigen loaded DC vaccine (Biological)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety]
时间窗: 3 months after the last vaccination injection
Safety of personalized neoantigen vaccine will be measured by the number of subjects experiencing each type of adverse event. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.
Immunogenicity of neoantigen-primed DC Vaccines
时间窗: once per three month
Immunogenicity of the DC vaccine will be measured to detect changes of neoantigen-specific T cells by flow cytometry.
次要结局
- Progression-free Survival (PFS)(up to 24 months after last dose of vaccine)
- Objective Response Rate(once per three months)
- Overall Survival (OS)(through study completion, an average of 1 year)