Clinical trial NCT03890198: A Phase 1 Study of LCAR-C182A Cells in the Treatment of Advanced Gastric Cancer and Pancreatic Ductal Adenocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Gastric Cancer
Pancreatic Ductal Adenocarcinoma
Keywords: Gastric cancer
Pancreatic Ductal Adenocarcinoma
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotech Co.
First posted: 2019-03-26
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: 90 days post infusion
measure: MTD）/ RP2D regimen finding
timeFrame: 90 days post infusion
measure: Transgene Levels of LCAR-C182A CAR-T Cells
timeFrame: 2 years post infusion
measure: Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
timeFrame: 2 years post infusion
measure: Systemic Cytokine Concentrations
timeFrame: 2 years post infusion
Secondary outcomes:
measure: Overall response rate (ORR) after administration
timeFrame: 2 years post infusion
measure: Duration of remission (DOR) after administration
timeFrame: 2 years post infusion
measure: Progress Free Survival (PFS) after administration
timeFrame: 2 years post infusion
measure: Overall Survival (OS) after administration
timeFrame: 2 years post infusion
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
state: Shanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Enxiao Li, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: