A Phase 1, Open-Label Study Evaluating the Safety, Tolerability and Efficacy of LCAR-C18S, an CAR-T Cell Therapy Targeting Claudin18.2 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 34
- 试验地点
- 3
- 主要终点
- Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
研究概览
简要总结
This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the cell-based LCAR-C18S (hereinafter "LCAR-C18S") in subjects with Claudin18.2-positive advanced solid Tumors.
详细描述
This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the cell-based LCAR-C18S (hereinafter "LCAR-C18S") in subjects with Claudin18.2-positive advanced solid Tumors. Patients who meet the eligibility criteria will receive LCAR-C18S infusion. The study will include the following sequential phases: screening, pre-treatment , treatment and follow up
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
- •The subjects have been fully informed of the possible risks and benefits of participating in the study and have signed the informed consent form;
- •Age 18-70 years;
- •Immunohistochemistry of tumor tissue samples indicates Claudin18.2 positive ;
- •Recurrent or metastatic advanced solid tumors (including advanced gastric cancers and non-gastric cancers) and have been failed to prior lines of systemic treatment
- •According to the RECIST v1.1, at least one measuable tumor lesion;
- •ECOG performance status score of 0-1;
- •Expected survival ≥ 3 months;
- •Subjects should have adequate organ functions before screening and treatment.
- •Women of childbearing age must have a negative blood pregnancy test; subjects of childbearing potential must use effective contraception for ≥ 1 year after the final study treatment.
排除标准
- •Previous CAR-T cell therapy or other cell therapies or therapeutic tumor vaccination against any target;
- •Any previous therapy targeting Claudin18.2;
- •Prior antitumor therapy with insufficient washout period;
- •Pregnant or lactating women;
- •Brain metastases with central nervous system symptoms;
- •Uncontrolled diabetes;
- •Oxygen is required to maintain adequate blood oxygen saturation;
- •Gastric perforation, pyloric obstruction, complete biliary obstruction, complete or incomplete intestinal obstruction requiring clinical intervention, or pleural effusion or peritoneal effusion requiring clinical intervention;
- •Clinically significant liver disorders (including liver cirrhosis, active viral hepatitis or other hepatitis);
- •HIV, Treponema pallidum or HCV serologically positive;
- •Severe underlying disease
- •New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50%; unstable angina, myocardial infarction or coronary artery bypass grafting (CABG) in the past 6 months; history of severe non-ischemic cardiomyopathy; or severe uncontrolled arrhythmia;
- •Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.
结局指标
主要结局
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
时间窗: Minimum 2 years after LCAR-C18S infusion (Day 1)
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
时间窗: 90 days post infusion
To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
Pharmacokinetic (PK) parameters
时间窗: Minimum 2 years after LCAR-C18S infusion (Day 1)
Blood samples will be collected for determination of cellular concentrations and transgenic levels of serum LCAR-C18S for pharmacokinetic analysis
次要结局
- Overall response rate (ORR) after administration(Minimum 2 years after LCAR-C18S infusion (Day 1))
- Overall Survival (OS) after administration(Minimum 2 years after LCAR-C18S infusion (Day 1))
- Progress Free Survival (PFS) after administration(Minimum 2 years after LCAR-C18S infusion (Day 1))
研究者
Jin Li
Director
Shanghai East Hospital