A Clinical Trial Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of IL-22BP/LNP Compound in Refractory Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence of Dose-Limiting Toxicities and Treatment Interruptions Due to Adverse Events During the First Cycle of IL-22BP/LNP Treatment
研究概览
简要总结
This study aims to investigate the safety and efficacy of the IL-22BP/LNP compound in patients with refractory malignant solid tumors, such as advanced soft tissue sarcoma, advanced head and neck squamous cell carcinoma, and malignant melanoma, who have failed second-line treatment, have advanced recurrence or metastatic malignant solid tumors.
详细描述
Cancer is a major cause of death among the global population and a significant obstacle to life extension. According to the statistics of the World Health Organization in 2019, it ranked as the first or second leading cause of death before the age of 70 in 112 countries, and in recent years, the burden of its incidence and mortality has increased rapidly. The treatment of advanced cancer consumes a large amount of resources, has poor efficacy, and is accompanied by numerous side effects. For example, the 5-year survival rate of advanced head and neck squamous cell carcinoma is only 40 - 50%, and radiotherapy may lead to osteonecrosis, while chemotherapy may cause hepatorenal toxicity and so on.
Against this background, researchers have been exploring better treatment options, and gene therapy has attracted much attention. Messenger RNA (mRNA) is a crucial part of gene therapy, and immune gene therapy holds great potential. Interleukin-22 (IL-22) influences tumor development, and IL-22 binding protein (IL-22BP) can block its activity and impede the proliferation of tumor cells.
Previously, there has been no research on mRNA vaccines targeting IL-22. Therefore, this project will provide a new treatment strategy for patients with advanced refractory malignant solid tumors.
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
- •Male or female patients: aged ≥ 18 years old and ≤ 70 years old;
- •Patients with histopathologically confirmed, refractory to second-line treatment, advanced recurrent/metastatic malignant solid tumors and without standard clinical treatment regimens (such as patients with advanced soft tissue sarcoma, advanced head and neck squamous cell carcinoma, malignant melanoma, etc.);
- •Eastern Cooperative Oncology Group (ECOG) performance status score: 0 - 1;
- •Expected survival time ≥ 3 months;
- •More than 28 days since the last chemotherapy/radiotherapy/surgery;
- •More than 6 weeks since the last use of nitrosoureas or mitomycin C;
- •Main organ functions are in good condition;
- •Sign a written informed consent form.
排除标准
- •Have participated in other drug clinical trials within 4 weeks;
- •The tumor is located close to major blood vessels or the trachea;
- •Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure of NYHA class II or above, unstable angina pectoris, having had a myocardial infarction within 1 year, and having clinically significant supraventricular or ventricular arrhythmias that require treatment or intervention.
- •For female subjects: pregnant or lactating women.
- •Patients have active tuberculosis, bacterial or fungal infections (≥ grade 2 of NCI-CTCAE 5.0); have active HIV infection, active HBV infection, or HCV infection.
- •Those with a history of psychotropic drug abuse who are unable to quit or have mental disorders;
- •Subjects have any active autoimmune diseases or a history of autoimmune diseases (such as, but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or those whose asthma in childhood has been completely relieved and who do not require any intervention in adulthood can be included; subjects with asthma that requires bronchodilators for medical intervention cannot be included).
- •Subjects are currently receiving immunosuppressive treatment.
- •Have a history of drug abuse or known medical, psychological, or social conditions, such as a history of alcoholism or drug use.
- •Known to be allergic, hypersensitive, or intolerant to the studied IL-22BP/LNP (including any excipients). Have a severe allergy history to any drugs, foods, or vaccines in the past, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, local allergic necrotizing reaction (Arthus reaction), etc.
- •From the screening period to 12 months after the completion of drug injection, female subjects have pregnancy plans or the partners of male subjects have pregnancy plans.
- •According to the investigator's judgment, there are concomitant diseases that seriously endanger patient safety or affect the patient's completion of the study.
研究组 & 干预措施
IL-22BP/LNP compound cohort
In this study, six patients were divided into two groups (n=3 per group), which received 25 μg or 50 μg of the IL-22BP/LNP compound, respectively. The treatment will be administered by intratumoral injection. Enrolled subjects will receive inoculations of IL-22BP/LNP compound injection according to their respective dose groups, which include 5 doses for basic immunization and subsequent personalized treatment. During the basic immunization, the first 4 doses will be given at an interval of 1 week each, and the 5th dose will be administered 1 month after the 4th dose. The entire course of treatment lasts for two months.
干预措施: IL-22BP mRNA vaccine injection (Biological)
结局指标
主要结局
Incidence of Dose-Limiting Toxicities and Treatment Interruptions Due to Adverse Events During the First Cycle of IL-22BP/LNP Treatment
时间窗: Participation in the whole process of the study.The entire treatment period lasts approximately 2 months.
Evaluate the incidence of dose-limiting toxicity (DLT) during the treatment with IL-22BP/LNP compound and the number of treatment interruptions due to treatment-related adverse reactions during the first treatment cycle.
次要结局
- Objective Response Rate(ORR)(From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.)
- Disease Control Rate (DCR)(From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.)
- Time to first complete remission (CR), partial remission (PR) on treatment with IL-22BP preparation.(From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.)
- Duration of Response(DOR)(From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected. The time window is approximately 2 months.)
- Duration of first confirmed disease stabilization(From the time when the patients were enrolled in the study until one month after the last dose of the IL-22BP/LNP compound was injected.The time window is approximately 2 months.)
- Progression - Free Survival(PFS)(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.)
- Overall Survival(OS)(From date of randomization until the date of death from any cause, assessed up to 36 months.)
研究者
Xingchen Peng
PhD, Professor
West China Hospital