NCT03890198终止早期 1 期
A Phase 1, Open-Label Study Evaluating the Safety, Tolerability and Efficacy of LCAR-C182A, an Anti-Claudin18.2 CAR-T Cell Therapy in Patients With Advanced Gastric Cancer and Pancreatic Ductal Adenocarcinoma
适应症
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Transgene Levels of LCAR-C182A CAR-T Cells
研究概览
简要总结
This is an open label, single center, single arm phase 1 study to evaluate the safety , tolerability, pharmacokinetics and efficacy and immunogenicity of LCAR-C182A cells targeting Claudin18.2 in the treatment of patients with advanced gastric cancer and Pancreatic Ductal Adenocarcinoma.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •the subject has fully understood the possible risks and benefits of participating in this study, and has signed informed consent form (ICF);
- •Age 18-75 years;
- •Histologically confirmed unresectable advanced gastric adenocarcinoma (including gastric esophageal junction adenocarcinoma) or advanced pancreatic ductal carcinoma;
- •Claudin18.2 positive by immunohistochemistry;
- •Previously accepted the recommendations of the national comprehensive cancer network (NCCN 2019 V1) or the gastric cancer guidelines of the cooperative professional committee on clinical oncology (CSCO 2018 V1) of the Chinese anti-cancer association, or the standard treatment regimen considered to be equivalent by the investigator；
- •Pancreatic cancer: ≥1 line standard chemotherapy, or regimens considered equivalent by the investigator, have recently failed or cannot be tolerated in the first line；
- •By CT scan or MRI, patients with a measurable lesion ≥1cm or a single lymph node with a short diameter ≥1.5cm (RECIST 1.1) are required to obtain permission from the principal investigator if the lesion is measurable, i.e. the target lesion is lymph node metastasis；
- •ECOG 0 ~ 1;
- •expected survival period≥ 3 months；
- •blood routine was in line with the certain standards；
- •blood biochemical test meets the certain criteria；
- •blood pregnancy test of women of child-bearing age was negative；
排除标准
- •has received CAR-T therapy targeting any target.
- •ever received any treatment targeting Claudin18.
- •brain metastasis with central nervous system symptoms;
- •pregnant or lactating women;
- •uncontrolled diabetes;
- •Oxygen absorption is required to maintain adequate blood oxygen saturation;
- •Patients with pyloric obstruction, gastric perforation, partial or complete intestinal obstruction and complete biliary obstruction that cannot be relieved after active treatment;
- •Hepatic disease;Chronic hepatitis infection with HBV/HCV;
- •Seropositive for human immunodeficiency virus (HIV);
- •Any active autoimmune disease or history of autoimmune disease;
- •have obvious bleeding tendency, such as gastrointestinal bleeding, coagulation dysfunction, and hypersplenism;
- •unstable angina within the past 6 months, symptomatic congestive heart failure or myocardial infarction;
- •severe uncontrolled arrhythmias;Left ventricular ejection fraction <50%;
- •activity requiring parenteral antibiotics or uncontrolled infection;There is evidence of severe active viral, bacterial or uncontrolled systemic fungal infection
- •other malignancies in the past 5 years except for non-melanoma skin cancer or in-situ cervical cancer;
- •chronic diseases treated with steroids or other immunosuppressive agents;
- •Concurrent use of hematopoietic growth factor;
- •Concurrent use of anticancer drugs or therapy (except radiotherapy for pain relief, etc., for non-target lesions);
- •Concurrent investigational treatment;
- •Have undergone chemotherapy, radiotherapy, or other experimental treatment within 4 weeks prior to apheresis
- •stroke or convulsion within 6 months before signing ICF;
- •Have received any live, attenuated vaccine within 4 weeks prior to apheresis;
- •Have underwent major surgical operation within 2 weeks prior to apheresis, or anticipate to undergo a major surgical operation during the study process or within 2 weeks posterior to study treatment (with the exception of anticipated local anesthesia surgery)
- •Allergic to the study drug expient and related expients (including but not limited to DMSO and dextran 40), or allergic to other immunotherapy and related drugs
- •Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
结局指标
主要结局
Transgene Levels of LCAR-C182A CAR-T Cells
时间窗: 2 years post infusion
Transgene Levels of LCAR-C182A CAR-T Cells using sensitive assay methods will be assessed
MTD）/ RP2D regimen finding
时间窗: 90 days post infusion
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
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
Number of Participants With Adverse Events
时间窗: 90 days post infusion
An adverse event is any untoward medical event that occurs in a participant administered an investigational product,and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Systemic Cytokine Concentrations
时间窗: 2 years post infusion
Serum cytokine concentrations such as IL-2, IL-6, IL-8, 1L-10, TNF-α, IFN-γ will be measured for biomarker assessment
次要结局
- Overall Survival (OS) after administration(2 years post infusion)
- Overall response rate (ORR) after administration(2 years post infusion)
- Progress Free Survival (PFS) after administration(2 years post infusion)
- Duration of remission (DOR) after administration(2 years post infusion)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
1 期
Investigation of the Safety and Tolerability of BSCT (Anti-nf-P2X7) 10% OintmentCarcinoma, Basal Cell (BCC)NCT02587819Biosceptre21
招募中
1 期
Antibody CC-1 in Men With Biochemical Recurrence of Prostate CancerProstate Cancer RecurrentNCT05646550University Hospital Tuebingen56
已完成
1 期
A Study to Evaluate Apatinib (Also Known as Rivoceranib) Plus Nivolumab in Participants With Unresectable or Metastatic CancerCancerNCT03396211Elevar Therapeutics30
招募中
1 期
SynOV1.1 Intratumoral Injection StudyHepatocellular CarcinomaNCT04612504Beijing Syngentech Co., Ltd.15
已完成
1 期
Assessment of KM-001 - Safety, Tolerability, and Efficacy in Patients With PPPK1 or PCPunctate Palmoplantar Keratoderma Type 1Pachyonychia CongenitaNCT05956314Kamari Pharma Ltd18