PD-1-M1-NK Cells in the Treatment of Advanced Gastric or Colorectal Cancer

NCT ID: NCT07031011

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-30
• Study Completion Date: 2027-06-30

Brief Summary

This is an Early Clinical Study to Investigate the Safety, Pharmacokinetics, and Efficacy of PD-1-M1-NK Cells (YC-T-001) in Patients with Advanced Gastric or Colorectal Cancer Failed or Intolerant to at Least Second-line Therapy.

Conditions

Advanced Gastric or Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Advanced gastric or colorectal cancer treated with PD-1-M1-CAR-NK Cells (YC-T-001)

Subjects with advanced gastric cancer or colorectal cancer were treated with PD-1-M1-CAR-NK Cells (YC-T-001) in the form of intraperitoneal injection

Group Type: EXPERIMENTAL

PD-1-M1-NK Cells

Intervention Type: BIOLOGICAL

At dose escalation stage, four dose groups were initially determined: 5×106CAR NK cells/kg, 1×107CARNK cells/kg, 2×107CARNK cells/kg, and 5×107 CARNK cells/kg. Administration cycle: In Cycle 1 (C1), the drug was administered once on days 1, 4, 7, 10 and 13 respectively. A complete cycle was formed by five consecutive administrations. For subjects with stable, partial response or complete response in the tumor assessment at the first time in week 4, the treatment in Cycle 2 will continue subsequently. In Cycle 2, the drug was administered once every two weeks (Q2W: D14±7 days and D28±7 days).

Interventions

PD-1-M1-NK Cells

At dose escalation stage, four dose groups were initially determined: 5×106CAR NK cells/kg, 1×107CARNK cells/kg, 2×107CARNK cells/kg, and 5×107 CARNK cells/kg. Administration cycle: In Cycle 1 (C1), the drug was administered once on days 1, 4, 7, 10 and 13 respectively. A complete cycle was formed by five consecutive administrations. For subjects with stable, partial response or complete response in the tumor assessment at the first time in week 4, the treatment in Cycle 2 will continue subsequently. In Cycle 2, the drug was administered once every two weeks (Q2W: D14±7 days and D28±7 days).

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Gender is not limited. Age should be between 18 and 75 years old (including the critical value), and one should be able to understand and voluntarily sign the informed consent form.

2. The ECOG performance status score is 0-1, and the expected survival period is no less than 3 months (judged by the researchers).

3. Advanced gastric cancer or colorectal cancer confirmed by histology, which has failed or been intolerant after at least two lines of standardized systematic treatment (including but not limited to targeted therapy, immunotherapy or chemotherapy), and has been confirmed as disease progression by imaging examination.

4. The subjects should be able to provide tumor tissue samples (archived tumor tissues within one year should be provided as much as possible) (at least 5-10 tumor tissue slices should be provided; if it is a surgical resection specimen, at least 10 slices should be provided). For patients in special circumstances who are unable to provide tissue samples or have less than 5 slices (or less than 10 surgical resection specimen slices), It is necessary to communicate with the partner to determine whether this selection criterion can be exempted. The tumor tissue samples were positive for PDL1+ by immunohistochemical detection.

5. There is at least one measurable lesion (in accordance with the RECIST 1.1 standard)

6. Unless otherwise specified, subjects should meet the following conditions before screening and pretreatment. If laboratory test abnormalities occur and do not meet the following standards, a re-examination within one week is allowed. If the standards are still not met, they will not be included:

1. Blood routine test (no intensive blood transfusion (such as more than 2 blood transfations within 7 days), platelet transfusion, cell growth factor (except recombinant erythropoietin) and other supportive treatments within 7 days before the test) : Neutrophils (NE) ≥ 1.5×109/L, lymphocytes (LY) ≥ 0.4×109/L (except before pretreatment), platelets (PLT) ≥ 75×109/L, hemoglobin (Hb) ≥ 8.0 g/dL;

2. Blood biochemistry: Endogenous creatinine clearance rate ≥ 50 mL/min (using the CockcrofT-GaulT formula), ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN, total bilirubin ≤ 2×ULN; Serum lipase and amylase ≤ 1.5 ULN; Alkaline phosphatase ≤ 2.5 ULN; If bone or liver metastasis occurs, AST, ALT and alkaline phosphatase ≤ 5ULN;

3. Prothrombin time (PT) ≤1.5×ULN; INR≤1.5×ULN; APTT≤1.5×ULN.

7. No active or uncontrolled central nervous system metastases (Patients with treated brain metastases who have stable symptoms and stable hormone doses for more than 4 weeks can be enrolled).

8. No active infection, including: negative HIV antibody; HBV-DNA and HCV-RNA were negative; Inactive tuberculosis There are no other active infections that require intravenous antibiotic treatment.

9. It was determined by the researchers that lymphocyte clearance therapy could be carried out.

10. If female subjects are fertile, effective contraceptive measures must be taken; Male subjects must take effective contraceptive measures during the treatment period and within 6 months after the treatment.

11. It is capable of performing normal venous blood collection and machine single blood collection, and can establish the venous access required for collection. There are no contraindications for white blood cell collection.

Exclusion Criteria

Central nervous system (CNS) metastasis, leptomeningeal disease or metastatic central compression; 2. Have a history of bone marrow or organ transplantation; 3. There is a history of other primary malignant tumors within 5 years before the study and treatment (except for cured cervical carcinoma in situ, thyroid cancer, localized basal cell carcinoma of the skin or squamous cell carcinoma); Those with two or more malignant tumors; 4. Those who meet any of the following: A. HIV infection (positive for HIV antibody); b. Active HBV infection (HBV DNA > 500 copies /ml or 100 IU/ml); c. Active HCV infection (positive for HCV antibody, positive for HCV-RNA); d. Syphilis infected individuals (TP-Ab positive); e. Subjects with known active pulmonary tuberculosis (TB); 5. Those who are allergic to any of the drug components used in the study (including but not limited to detoxification drugs); 6. Patients who have received cell therapy previously; 7. Adverse events of previous anti-tumor treatments have not yet recovered to grade ≤1 in the CTCAE 5.0 rating before administration (except for toxicities judged by the investigator as having no safety risks, such as alopecia, pigmentation, grade 2 peripheral neurotoxicity, and stable hypothyroidism after hormone replacement therapy, etc.); 8. There was an uncontrolled active infection within 4 weeks before signing the informed consent form, and parenteral antibiotic, antiviral or antifungal treatment was required; 9. Have a history of interstitial lung disease or interstitial pneumonia, either concomitant or in the past; 10. Suffering from active or potentially recurrent autoimmune diseases; 11. Have received systemic corticosteroid (prednisone > 10mg/ day or equivalent doses of similar drugs) or other immunosuppressant therapy within 14 days prior to the first use of the study drug (except in the following circumstances: allowing local, ocular, intra-articular, intranasal and inhaled corticosteroid therapy; Short-term use of corticosteroids for preventive treatment, such as preventing contrast agent allergy; Glucocorticoid patients with physiological replacement therapy doses; 12. Abnormal laboratory tests: Absolute neutrophil count < 1.5×10^9/L; Platelet count < 75×10^9/L; Hemoglobin < 80g/ ALT or AST> 2.5×ULN; Total bilirubin > 2×ULN; Serum creatinine clearance rate < 60mL/min; 13. There was bleeding requiring medical intervention within 4 weeks before signing the informed consent form, including esophageal variceal bleeding; 14. Have received attenuated/inactivated vaccines within 4 weeks after signing the informed consent form, or plan to receive attenuated/inactivated vaccines during the screening period; Or have received attenuated/inactivated vaccines within two weeks before clearing the forest; 15. Have received anti-tumor treatments such as systemic chemotherapy, radiotherapy, targeted therapy, endocrine therapy, biological therapy and immunotherapy within 4 weeks before the first use of the study drug, except for the following: Nitrosyrea or mitomycin C within 6 weeks before the first use of the study drug; Oral fluorouracil, small molecule targeted drugs and traditional Chinese medicines with anti-tumor indications were taken within two weeks before the first use of the study drugs. Local palliative radiotherapy is within 2 weeks before the first use of the study drug; 16. Have received other unmarketed clinical research drugs or treatments within 4 weeks before the first use of the investigational drug; 17. Had undergone major organ surgery (excluding puncture biopsy diagnostic treatment) or suffered severe trauma within 4 weeks before the first use of the study drug, or required elective surgery during the trial; 18. There were severe non-healing wounds/ulcers/fractures, etc. within 4 weeks before the first use of the study drug; 19. Have a serious history of cardiovascular and cerebrovascular diseases, including but not limited to:

1. There are severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second-to-third-degree atrioventricular block, etc.

2. Those with grade II to IV cardiac insufficiency according to the standards of the New York Heart Association (NYHA) in the United States;

3. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or above cardiovascular and cerebrovascular events occurred within 6 months before the first administration;

4. Clinically uncontrollable hypertension (blood pressure still cannot be controlled at systolic blood pressure < 140 mmHg and/or diastolic blood pressure < 90 mmHg after antihypertensive treatment);

5. Any factors that increase the risk of prolonged QTc or arrhythmia, such as heart failure, uncorrected hypokalemia, congenital long QT syndrome, or the need to use any concomitant drugs known to prolong the QT interval; 20. It is known that uveitis of grade ≥ 2 and retinopathy, etc. 21.. Known, recorded or suspected drug abuse subjects; 22. Pregnant or lactating women; 23. The researchers believe that the subjects have mental disorders, poor compliance, intolerance to apheresis, a history of other serious systemic diseases, or other reasons and are not suitable to participate in this clinical study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

jiuwei cui

OTHER

Sponsor Role: lead

Responsible Party

jiuwei cui

Chief Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Cancer Center, The First Affiliated Hospital of Jilin University

Changchun, Jilin, China

Countries

China

Central Contacts

jiuwei Cui

Role: CONTACT

jdyycjw@163.com

15843073215

Facility Contacts

jiuwei Cui

Role: primary

jdyycjw@163.com

15843073215

Other Identifiers

YC-T-001

Identifier Type: -

Identifier Source: org_study_id