Clinical trial NCT06464965: Clinical Study of Cord Blood-Derived CAR-NK Cells in Gastric Cancer and Pancreatic Cancer
Official title: A Phase I Clinical Study of Cord Blood-Derived CAR-NK Cells Targeting Claudin18.2 in the Treatment of Advanced Gastric Cancer and Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastric Cancer
Pancreas Adenocarcinoma
Keywords: Gastric Cancer
Pancreatic Adenocarcinoma
CAR-NK
Claudin18.2
Lead sponsor: Zhejiang Provincial People's Hospital
Sponsor class: OTHER
Collaborators: name: Zhejiang University
name: Hangzhou RongGu Biotechnology Limited Company
First posted: 2024-06-18
Enrollment: 30
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: 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;


Eligibility criteria: 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.

Primary outcomes:
measure: MTD
timeFrame: 3 years
measure: DLT
timeFrame: 3 years
Secondary outcomes:
measure: ORR
timeFrame: 3 years
measure: DCR
timeFrame: 3 years
measure: PFS
timeFrame: 3 years
measure: OS
timeFrame: 3 years
measure: DOR
timeFrame: 3 years
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Provincial People's Hospital
state: Zhejiang
Study officials:
affiliation: Zhejiang Provincial People's Hospital
name: Yang Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
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