Clinical Study of Cord Blood-Derived CAR-NK Cells in Gastric Cancer and Pancreatic Cancer

Phase 1

Recruiting

• Conditions: Gastric Cancer; Pancreas Adenocarcinoma
• Interventions: Biological: CB CAR-NK182

• Registration Number: NCT06464965
• Lead Sponsor: Zhejiang Provincial People's Hospital

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;

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-06-13
• Study First Submitted QC: 2024-06-13
• Study First Posted: 2024-06-18
• Status Verified: 2024-07
• Study Start: 2024-07-19
• Last Update Submitted: 2024-07-29
• Last Update Posted: 2024-07-31
• Primary Completion: 2025-06-13
• Study Completion: 2027-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CB CAR-NK182	CB CAR-NK182	Set 3 dose groups: dose group 1(2 × 10\^6/kg/time, cell infusion on days 0,7 and 14, respectively, 3 times in total), dose group 2(4 × 10\^6/kg/time, cell infusion on days 0,7 and 14, respectively, 3 times in total), dose group 3(8 × 10\^6/kg/time, cell infusions were performed on days 0,7 and 14, respectively, for a total of 3 times). Each dose will enroll 3-6 subjects, each subject will be observed for at least 28 days after receiving the first dose, and the long-term follow-up period will be 2 years after each patient's first dose infusion.

Primary Outcome Measures

Name	Time	Method
DLT	3 years	Dose-Dependent Toxicity
MTD	3 years	Maximum Tolerated Dose

Secondary Outcome Measures

Name	Time	Method
OS	3 years	overall survival
DOR	3 years	duration of response
DCR	3 years	Disease control rate
PFS	3 years	progression-free survival
ORR	3 years	Overall objective tumor response rate

Trial Locations

Locations (1)

Zhejiang Provincial People's Hospital; 🇨🇳 Hangzhou, Zhejiang, China