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
Overview
- Phase
- Early Phase 1
- Intervention
- Not specified
- Conditions
- Gastric Cancer
- Sponsor
- First Affiliated Hospital Xi'an Jiaotong University
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Transgene Levels of LCAR-C182A CAR-T Cells
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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；
Exclusion Criteria
- •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;
Outcomes
Primary Outcomes
Transgene Levels of LCAR-C182A CAR-T Cells
Time Frame: 2 years post infusion
Transgene Levels of LCAR-C182A CAR-T Cells using sensitive assay methods will be assessed
MTD）/ RP2D regimen finding
Time Frame: 90 days post infusion
Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
Time Frame: 2 years post infusion
Venous blood samples will be collected for measurement of CAR-T positive cellular concentration
Number of Participants With Adverse Events
Time Frame: 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
Time Frame: 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
Secondary Outcomes
- 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)