A Phase 1 Study of LCAR-C182A Cells in the Treatment of Advanced Gastric Cancer and Pancreatic Ductal Adenocarcinoma

NCT03890198 | Terminated Early Phase 1

• 1 other identifier: MO-GPC01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer; Pancreatic Ductal Adenocarcinoma

Keywords

Gastric cancer; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Adverse Events

  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.

  90 days post infusion

• MTD）/ RP2D regimen finding

  Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

  90 days post infusion

• Transgene Levels of LCAR-C182A CAR-T Cells

  Transgene Levels of LCAR-C182A CAR-T Cells using sensitive assay methods will be assessed

  2 years post infusion

• Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration

  Venous blood samples will be collected for measurement of CAR-T positive cellular concentration

  2 years post infusion

• Systemic Cytokine Concentrations

  Serum cytokine concentrations such as IL-2, IL-6, IL-8, 1L-10, TNF-α, IFN-γ will be measured for biomarker assessment

  2 years post infusion

Secondary Outcomes (4)

• Overall response rate (ORR) after administration

  2 years post infusion

• Duration of remission (DOR) after administration

  2 years post infusion

• Progress Free Survival (PFS) after administration

  2 years post infusion

• Overall Survival (OS) after administration

  2 years post infusion

Study Arms (1)

chimeric Antigen Receptor T cell

EXPERIMENTAL

LCAR-C182A Cells

Biological: LCAR-C182A cells

Interventions

LCAR-C182A cells BIOLOGICAL

Patients receive fludarabine (3×300 mg/ m\^2) and cyclophosphamide (3×30 mg/m\^2) IV on days -5 to-3, and then Patients receive CAR-T cells. PS：The specific dose of fludarabine and cyclophosphamide is adjusted according to the individual condition of the subject and the judgment of the investigator.

chimeric Antigen Receptor T cell

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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；

You may not qualify if:

• has received CAR-T therapy targeting any target.
• ever received any treatment targeting Claudin18.2.
• 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;

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• Nanjing Legend Biotech Co.: collaborator

Study Sites (1)

The First Affiliated Hospital of Xian Jiaotong University

Xi’an, Shanxi, 710004, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Enxiao Li, MD,PhD

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2019
• First Posted: March 26, 2019
• Study Start: April 22, 2019
• Primary Completion: March 6, 2020
• Study Completion: March 6, 2020
• Last Updated: July 2, 2020

Record last verified: 2020-06

Locations

CN (1)