A Phase 1, Open-Label Study Evaluating the Safety, Tolerability and Efficacy of (LCAR)-G08, a Chimeric Antigen Receptor (CAR)-T Cell Therapy Targeting Guanylyl Cyclase C (GCC) in Subjects With Advanced Gastrointestinal Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Maximum concentration (Cmax)
研究概览
简要总结
This is a phase 1, single-arm, open-label, dose escalation and expansion study of LCAR-G08 in adult subjects with advanced gastrointestinal tumors expressing guanylyl cyclase C (GCC).
详细描述
This is a phase 1, single-arm, open-label, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the cell-based LCAR- G08 in subjects with guanylyl cyclase C (GCC)-positive advanced gastrointestinal tumors. Subjects who meet the eligibility criteria will receive LCAR-G08 infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), 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
盲法说明
Masking Description
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
- •Voluntary agreement to provide written informed consent.
- •Histologically confirmed metastatic colorectal cancers and other advanced gastrointestinal cancers (esophageal cancer, gastric cancer, pancreatic cancer, and small bowel cancer).
- •Aged 18 to 70 years, either sex.
- •GCC immunohistochemistry (IHC) staining is positive.
- •At least one measurable tumor lesion according to RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Expected survival ≥ 3 months.
- •Clinical laboratory values meet screening visit criteria.
排除标准
- •Previous CAR-T cell, T cell receptor-engineered (TCR) T cell, or therapeutic tumor vaccination treatment within the past 6 months; and the corresponding CAR-T, TCR-T cells can still be detected.
- •Ever received any treatment targeting GCC.
- •Prior antitumor therapy with insufficient washout period.
- •Brain metastases.
- •Pregnant or lactating women.
- •Hepatitis C virus (HCV) antibody-positive or human immunodeficiency virus (HIV) antibody-positive, active syphilis, Epstein-Barr virus (EBV) infected.
- •Severe underlying disease.
- •Presence of other serious pre-existing medical conditions that may limit patient participation in the study.Any condition that, in the investigator's judgment, will make the subject unsuitable for participation in this study.
- •Any condition that, in the investigator's judgment, will make the subject unsuitable for participation in this study.
研究组 & 干预措施
Chimeric Antigen Receptor T cell LCAR-G08 Cells
Each subject will receive LCAR-G08 Cells
干预措施: LCAR-G08 cells (Biological)
结局指标
主要结局
Maximum concentration (Cmax)
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
The maximum observed concentration of CAR positive T cells or transgene CAR copy number after LCAR-G08 infusion.
Time to Cmax (Tmax)
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
The time it takes to reach the maximum concentration or time to Cmax after LCAR-G08 infusion.
Recommended Phase 2 Dose (RP2D) regimen finding
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
RP2D established through accelerated titration design (ATD) and Bayesian Optimal Interval (BOIN) design.
Dose-limiting toxicity (DLT) rate
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
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.
Time to the last observed concentration
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
The time it takes to reach the last observed concentration after LCAR-G08 infusion.
Area Under the Curve (AUC) last
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
The total exposure of the drug experienced by the subject in a clinical study from LCAR-G08 infusion to time to the last observed concentration.
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
时间窗: Minimum 2 years after LCAR-G08 infusion (Day 1)
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.
次要结局
- Progression-free Survival (PFS) after administration(Minimum 2 years after LCAR-G08 infusion (Day 1))
- Time to Response (TTR) after administration(Minimum 2 years after LCAR-G08 infusion (Day 1))
- Incidence of anti-LCAR-G08 antibody and positive sample titer(Minimum 2 years after LCAR-G08 infusion (Day 1))
- Disease Control Rate (DCR) after administration(Minimum 2 years after LCAR-G08 infusion (Day 1))
- Objective Response Rate (ORR) after administration(Minimum 2 years after LCAR-G08 infusion (Day 1))
- Duration of Remission (DoR) after administration(Minimum 2 years after LCAR-G08 infusion (Day 1))
- Overall Survival (OS) after administration(Minimum 2 years after LCAR-G08 infusion (Day 1))
研究者
Shen Lin
Professor
Peking University