Gastric Cancer, Pancreas Adenocarcinoma
Conditions
Keywords
Gastric Cancer, Pancreatic Adenocarcinoma, CAR-NK, Claudin18.2
Brief summary
Main Objective: To study the maximum tolerated dose (MTD) and dose-dependent toxicity (DLT) of cord blood-derived CAR-NK cells (CB CAR-NK182) targeting Claudin18.2 in patients with advanced gastric cancer and advanced pancreatic cancer. Secondary Objective: To evaluate the efficacy of CB CAR-NK182 in patients with advanced gastric cancer and advanced pancreatic cancer: overall objective tumor response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), etc. To evaluate the CAR-NK amplification and persistence of CB CAR-NK182 in the blood of patients with advanced gastric cancer and advanced pancreatic cancer;
Interventions
BIOLOGICALCB CAR-NK18.2
Administered via intravenous infusion on Days 0, 3, and 7. Three dose levels are planned: Dose Level 1: 2×10\^6 cells/kg/infusion Dose Level 2: 8×10\^6 cells/kg/infusion Dose Level 3: 16×10\^6 cells/kg/infusion
DRUGCyclophosphamide
Part of the lymphodepletion regimen. Administered at 500 mg/m\^2/day on Days -5 to -3 prior to the first CAR-NK cell infusion.
DRUGFludarabine
Part of the lymphodepletion regimen. Administered at 30 mg/m\^2/day on Days -5 to -3 prior to the first CAR-NK cell infusion.
Sponsors
Zhejiang Provincial People's Hospital
Zhejiang University
Hangzhou RongGu Biotechnology Limited Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 18-75 years (inclusive); 2. Understands and voluntarily signs a written informed consent form, and is willing and able to comply with all trial requirements; 3. Patients with advanced gastric cancer and advanced pancreatic cancer confirmed by histopathology or cytology, who have failed standard treatment or cannot tolerate standard treatment, including but not limited to: pancreatic cancer and gastric cancer; 4. Immunohistochemical (IHC) detection of CLDN18.2, the positive expression of CLDN18.2 in tumors must be ≥ 10%; 5. At least 1 measurable lesion according to RECIST 1.1; 6. ECOG score is 0-1; 7. All toxic reactions caused by previous antineoplastic therapy were resolved to grade 0-1 (according to NCI CTCAE 5.0 edition); Expected survival ≥ 12 weeks; In addition to the primary disease, no serious hematology, heart and lung, liver and kidney disease, laboratory tests meet the following requirements: Peripheral blood neutrophil absolute value ≥ 2000/mm3, platelet ≥ 50000/mm3 Serum creatinine ≤ 1.5mg/dL;ALT (alanine aminotransferase)/AST (aspartate aminotransferase) below 2.5 times the upper limit of normal; Total bilirubin ≤ 1.5mg/dL; Cardiac ejection fraction (EF)≥ 50%; International standard ratio (INR) or prothrombin time (PT) below 1.5 times the upper limit of normal; Activated partial coagulation time (aPTT) below 1.5 times the upper limit of normal; 10. Women of childbearing potential must have a negative serum pregnancy test and agree to effective birth control during the treatment phase and within 12 months after injection of CAR-NK cells; Male patients must agree to use effective birth control during the study and for 12 months after injection of CAR-NK cells.
Exclusion criteria
1. History of other tumors; 2. Patients who have received CAR-T,CAR-NK,TCR-T and other cell therapy targeting Claudin18.2 within 3 months before study treatment; 3. Patients with hypersensitivity to cell therapy or any related drugs; 4. Active autoimmune diseases; 5. Active infections that cannot be controlled; 6. HIV infection, uncontrolled HBV, HCV and syphilis infections; 7. Have metastatic disease of the central nervous system (CNS), leptomeningeal disease or spinal cord compression; 8. Patients with severe heart disease; 9. Patients with unstable/active ulcers or bleeding from the digestive system; 10. Patients with a history of bleeding or bleeding tendency in the digestive system; 11. Pregnant or lactating women; 12. There are other factors that the researcher believes are not suitable for participating in the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | 1 month | Maximum Tolerated Dose |
| DLT | 1 month | Dose-Dependent Toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 3 years | Overall objective tumor response rate |
| DCR | 3 years | Disease control rate |
| PFS | 3 years | progression-free survival |
| OS | 3 years | overall survival |
| DOR | 3 years | duration of response |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYang Liu, M.D.
Zhejiang Provincial People's Hospital
Outcome results
None listed