A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-M23, a CAR-T Cell Therapy Targeting MSLN in Patients With Relapsed and Refractory Epithelial Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This study is a prospective, single-arm, open-label, single-dose dose finding and extension study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the LCAR-M23 CAR-T cell therapy in subjects with relapsed and refractory epithelial ovarian cancer after prior adequate standard of care.
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
- Female
- 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 this study and have voluntarily signed the informed consent form (ICF)
- •Age: 18-70 years (including 18 and 70 years)
- •Female subjects with histologically or cytologically confirmed advanced epithelial ovarian cancer including fallopian tube and primary peritoneal cancers
- •Mesothelin (MSLN) positive
- •Prior adequate standard of care, treatment failure or intolerance.
- •Imaging shows an evaluable tumor lesion
- •Expected survival ≥ 3 months
排除标准
- •Patients who have received the following anti-tumor treatments prior to apheresis:
- •Cytotoxic therapy within 14 days
- •Small molecule targeted therapy within 14 days or at least 5 half-lives, whichever is shorter
- •Therapy with monoclonal antibody within 21 days
- •Immunomodulatory therapy within 7 days
- •Radiotherapy within 14 days and endocrine therapy within 14 days (including tamoxifen, aromatase inhibitor, high-potency progesterone and gonadotropin-releasing hormone analogue, etc.)
- •Previously treated with CAR-T/TCR-T cell therapy against any target or other cell therapies or therapeutic tumor vaccine
- •Previously treated with any MSLN-targeted therapy
- •Brain metastases with central nervous system symptoms
- •Pregnant or lactating women
- •Any condition in which, in the opinion of the investigator, the subject is ineligible for participation in the study
结局指标
主要结局
Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: 90 days post infusion
Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose. An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment.
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
时间窗: 2 years post infusion
Venous blood samples will be collected for measurement of CAR-T positive cellular concentration
MTD/ RP2D regimen finding
时间窗: 90 days post infusion
Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)
次要结局
- Objective Response Rate (ORR) after administration(2 years post infusion)
- Overall Survival (OS) after administration(2 years post infusion)
- Progress Free Survival (PFS) after administration(2 years post infusion)
- Time to Response (TTR) after administration(2 years post infusion)
- Duration of Response (DOR) after administration(2 years post infusion)
- Disease control rate (DCR) after administration(2 years post infusion)