Trial Title:
Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells for Gastric/Gastroesophageal Junction Adenocarcinoma
NCT ID:
NCT06353152
Condition:
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Esophageal Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection
Description:
single-/multiple-dose infusion
Arm group label:
Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection
Summary:
A single-arm, open-label early-stage exploratory clinical study to evaluate the safety,
tolerability and efficacy of Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells in
subjects with gastric/gastroesophageal junction adenocarcinoma.
Detailed description:
This study is an open-label, single-/multiple-dose infusion, adaptive dose-escalation
designed early exploratory clinical trial aiming to evaluate the safety, tolerability,
and efficacy of Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Injection in
subjects with CLDN18.2 positive and pathologically confirmed locally advanced or
metastatic gastric/gastroesophageal junction adenocarcinoma.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age: 18-70 years old (including the threshold);
2. Subject has pathologically confirmed locally advanced or metastatic
gastric/gastroesophageal junction adenocarcinoma：Having received at least one
standard treatment, with the disease in stable or progressive state, and the subject
refusing further treatment or intolerant to existing therapies; Failing second-line
treatment;
3. Subject's freshly biopsied tumor tissue (if the patient has not received targeted
Claudin18.2 therapy, archived tumor tissue within one year is acceptable) has
immunohistochemistry confirmed positive expression of Claudin18.2;
4. Subject has predicted life expectancy ≥ 90 days;
5. Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
6. Subject is willing to undergo tumor biopsy;
7. Subject has at least one measurable tumor lesion on imaging (per RECIST 1.1
criteria);
8. Female subjects of childbearing age must not be lactating, and sensitive serum
pregnancy test during the screening period must be negative for fertile women. All
subjects must use medically accepted contraceptive measures (such as intrauterine
devices, contraceptives) throughout the treatment period and 1 year after cell
infusion. Male subjects must also avoid sperm donation;
9. Subject has adequate organ function reserves: Absolute neutrophil count (ANC) ≥
1.5×109/L; Absolute lymphocyte count (ALC) ≥ 0.6×109/L; Platelet count ≥ 75×109/L;
Hemoglobin ≥ 9.0 g/dL; Total bilirubin ≤ 2 × upper limit of normal (ULN) ; ALT and
AST ≤ 2.5 × ULN (or ≤ 5 × ULN if bone or liver metastases are present); Creatinine
clearance (Cockcroft-Gault method) ≥ 60 mL/min; Stable coagulation function:
Prothrombin time (PT) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤
1.5 × ULN; Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 55%
without moderate or severe pericardial effusion; Baseline oxygen saturation in room
air ≥ 92%;
10. Subject is able to establish intravenous access, and peripheral blood mononuclear
cells can be collected according to the investigator's judgment;
11. Subject is willing to sign the informed consent form;
12. Subject can communicate well with the investigator, is willing and able to comply
with the study plan and will complete the study as per the study requirements.
Exclusion Criteria:
1. Subject has a positive test for Hepatitis B surface antigen (HBsAg) or Hepatitis C
virus antibody (HCV-Ab) or Treponema pallidum antibody (TP-Ab) or Human
Immunodeficiency Virus antibody (HIV-Ab). Subjects who are positive for both
hepatitis B core antibody (HBcAb) and HBV deoxyribonucleic acid (DNA) will be
excluded.
2. Subject has other malignant tumors, except for: cured non-melanoma skin cancer, in
situ cervical carcinoma, localized prostate cancer, superficial bladder cancer,
ductal carcinoma in situ, and other malignant tumors with disease-free survival
exceeding 5 years.
3. Subject has symptomatic intracranial metastases.
4. Subject has central or extensive lung or liver metastases.
5. Subject with a maximum target lesion > 4.0 cm (per RECIST 1.1 criteria).
6. The subjects' tumor tissue is positive for HER2 expression.
7. Subject has a history of prior anti-tumor treatment or participation in clinical
trials: subject has received treatment with CAR-T therapy, or other gene-edited cell
therapies; subject has participated in other clinical trials within 28 days before
screening; Subject has received local radiotherapy or small molecule chemotherapy
within 7 days before leukapheresis, or within at least five half-lives (whichever is
longer).; subject has received daily systemic corticosteroid ≥ 15 mg within 7 days
before leukapheresis, except inhaled corticosteroids.
8. Subject has received vaccination within 28 days before screening.
9. Subject has conditions requiring the use of systemic corticosteroids or other
immunosuppressive drugs during the study period, as determined by the investigator.
10. Subject has acute toxic reactions from previous treatments not recovered to Grade 1
or lower (excluding hematological toxicity, alopecia, and events considered
tolerable by the investigator).
11. Subject has life-threatening hypersensitivity reactions or other intolerances to
cyclophosphamide, fludarabine, or albumin-bound paclitaxel, or severe
hypersensitivity to human serum albumin, DMSO, or other substances.
12. Subject underwent general anesthesia within 28 days before screening, or has not
recovered and clinically stabilized after previous surgical treatment, or is
expected to undergo general anesthesia during the study.
13. Subject has any unstable cardiovascular diseases within 180 days before screening,
including but not limited to unstable angina, myocardial infarction, heart failure
(New York Heart Association [NYHA] class ≥ III), severe arrhythmias requiring
medication, or underwent cardiovascular intervention, coronary artery stenting, or
coronary artery bypass grafting within 180 days before screening.
14. Subject has a disease or history of central nervous system disorders, such as
epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any
autoimmune diseases involving the CNS.
15. Subject has uncontrolled or requiring intravenous treatment for fungal, bacterial,
viral, or other infections at the time of screening.
16. Subject has uncontrolled or active ulcers or gastrointestinal bleeding at the time
of screening.
17. Subject has active autoimmune diseases (including but not limited to systemic lupus
erythematosus, Sjögren's syndrome, rheumatoid arthritis, psoriasis, multiple
sclerosis, inflammatory bowel disease, Hashimoto's thyroiditis, etc., with the
exception of hypothyroidism that can be controlled only by hormone replacement
therapy).
18. Subject has a bleeding and thrombotic tendency, including: subject who had
significant clinically significant bleeding symptoms or definite bleeding tendencies
within 90 days before screening, subject who has genetic or acquired bleeding and
thrombotic tendencies (e.g., hemophilia, coagulation disorders, splenic
hyperfunction), subject who is undergoing thrombolysis or anticoagulant therapy and
subject who had events of arterial/venous thrombosis within 180 days before
screening, such as cerebrovascular disease (including cerebral hemorrhage, cerebral
infarction), deep venous thrombosis, and pulmonary embolism.
19. Subject has a history of substance abuse with psychiatric drugs and unable to
abstain, or with a history of psychiatric disorders.
20. Subject has other situations in which the investigator deems unsuitable for
participation in this clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Zip:
100142
Country:
China
Status:
Recruiting
Contact:
Last name:
Shen Lin, Professor
Phone:
010-88196561
Email:
doctorshenlin@sina.cn
Investigator:
Last name:
Shen Lin, professor
Email:
Principal Investigator
Start date:
November 17, 2023
Completion date:
November 16, 2025
Lead sponsor:
Agency:
Peking University
Agency class:
Other
Collaborator:
Agency:
Gracell Biopharmaceuticals, Inc.
Agency class:
Industry
Source:
Peking University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06353152
