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

NCT ID: NCT03890198

Last Updated: 2020-07-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-22
• Study Completion Date: 2020-03-06

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

chimeric Antigen Receptor T cell

LCAR-C182A Cells

Group Type: EXPERIMENTAL

LCAR-C182A cells

Intervention Type: 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.

Interventions

LCAR-C182A cells

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. the subject has fully understood the possible risks and benefits of participating in this study, and has signed informed consent form (ICF);

2. Age 18-75 years;

3. Histologically confirmed unresectable advanced gastric adenocarcinoma (including gastric esophageal junction adenocarcinoma) or advanced pancreatic ductal carcinoma;

4. Claudin18.2 positive by immunohistochemistry;

5. 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；

6. Pancreatic cancer: ≥1 line standard chemotherapy, or regimens considered equivalent by the investigator, have recently failed or cannot be tolerated in the first line；

7. 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；

8. ECOG 0 ~ 1;

9. expected survival period≥ 3 months；

10. blood routine was in line with the certain standards；

11. blood biochemical test meets the certain criteria；

12. blood pregnancy test of women of child-bearing age was negative；

Exclusion Criteria

1. has received CAR-T therapy targeting any target.

2. ever received any treatment targeting Claudin18.2.

3. brain metastasis with central nervous system symptoms;

4. pregnant or lactating women;

5. uncontrolled diabetes;

6. Oxygen absorption is required to maintain adequate blood oxygen saturation;

7. Patients with pyloric obstruction, gastric perforation, partial or complete intestinal obstruction and complete biliary obstruction that cannot be relieved after active treatment;

8. Hepatic disease;Chronic hepatitis infection with HBV/HCV;

9. Seropositive for human immunodeficiency virus (HIV);

10. Any active autoimmune disease or history of autoimmune disease;

11. have obvious bleeding tendency, such as gastrointestinal bleeding, coagulation dysfunction, and hypersplenism;

12. unstable angina within the past 6 months, symptomatic congestive heart failure or myocardial infarction;

13. severe uncontrolled arrhythmias;Left ventricular ejection fraction <50%;

14. activity requiring parenteral antibiotics or uncontrolled infection;There is evidence of severe active viral, bacterial or uncontrolled systemic fungal infection

15. other malignancies in the past 5 years except for non-melanoma skin cancer or in-situ cervical cancer;

16. chronic diseases treated with steroids or other immunosuppressive agents;

17. Concurrent use of hematopoietic growth factor;

18. Concurrent use of anticancer drugs or therapy (except radiotherapy for pain relief, etc., for non-target lesions);

19. Concurrent investigational treatment;

20. Have undergone chemotherapy, radiotherapy, or other experimental treatment within 4 weeks prior to apheresis

21. stroke or convulsion within 6 months before signing ICF;

22. Have received any live, attenuated vaccine within 4 weeks prior to apheresis;

23. 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)

24. 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

25. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing Legend Biotech Co.

INDUSTRY

Sponsor Role: collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Enxiao Li, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital Xi'an Jiaotong University

Locations

The First Affiliated Hospital of Xian Jiaotong University

Xi’an, Shanxi, China

Countries

China

Other Identifiers

MO-GPC01

Identifier Type: -

Identifier Source: org_study_id