NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer

NCT05213195 | Recruiting Phase 1

• 1 other identifier: CARNK-002
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer

Conditions

Refractory Metastatic Colorectal Cancer

Keywords

Refractory Metastatic Colorectal Cancer; NKG2D; CAR-NK

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity#DLT#

  Safety

  28 days

• Maximal Tolerable Dose#MTD#

  tolerability evaluation

  28 days

Secondary Outcomes (3)

• Antitumor efficacy-Duration of response (DOR)

  52 weeks

• Antitumor efficacy-Objective response rate (ORR)

  52 weeks

• Antitumor efficacy-Overall survival (OS)

  52 weeks

Study Arms (1)

NKG2D CAR-NK

EXPERIMENTAL

NKG2D CAR-NK Cell Therapy in Patients With Refractory Metastatic Colorectal Cancer Will be intra-peritoneal infusion in Stage 1 and combined with intra-venous infusion in Stage 2. While in Stage 3, the investigators will expand to other cancer type at certain situation

Drug: NKG2D CAR-NK

Interventions

NKG2D CAR-NK DRUG

NKG2D CAR-NK infusion through peritoneal in stage 1 and later combined with intra venous in stage 2.

Also known as: Natural killer group 2 member D (NKG2D) ligand-targeting chimeric antigen receptor (CAR) natural killer (NK) cells

NKG2D CAR-NK

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 70 years (including boundary values), both male and female.
• Patients with advanced colorectal cancer with abdominal metastasis who had previously failed standard therapy and no other feasible and effective treatment was available.
• The expected survival period of the subject is ≥12 weeks.
• Subjects should have at least one target lesion that can be assessed stably by CT or MRI according to RECIST V.1.1.
• The target lesions had measurable diameter lines (tumor lesions with CT scan length ≥10 mm, lymph node lesions with CT scan short diameter ≥10 mm 15 mm, scanning layer thickness is no more than 5 mm). Or by laparoscopy, at least one of them had PCI scores Accurate, assessable target lesions.
• \. ECOG physical status score is 0 \~ 1.
• \. Subject has adequate organ and bone marrow function. Laboratory screening must meet the following criteria for all laboratory tests Results should be within the stable range described below and without continuous supportive treatment.
• Blood test: WBC≥ 1.5×109/L; Platelet count PLT ≥60×109/L; Hemoglobin content Hb 8.0 g/dL or higher; Lymphocyte LYM≥0.4×109/L;
• Blood biochemistry: serum creatinine ≤1.5 ×ULN, if serum creatinine \> 1.5 ×ULN, creatinine clearance rate \> 50mL/min (calculated according to the Cockcroft-Gault formula); Serum total bilirubin ≤1.5×ULN, ALT≤2 ×ULN, AST≤ 2 ×ULN (liver metastasis or liver cancer patients) ALT≤5 x ULN, AST≤5 x ULN).
• Amylase and lipase ≤ 1.5 × ULN;
• Routine urine examination: urinary protein \< 2+.
• \. Left ventricular ejection fraction (LVEF) \> 45% by color doppler echocardiography within one month
• \. Fertility status: Female patients of reproductive age or male patients with sexual partners of female patients of reproductive age are willing to sign informed consent,Use effective contraception from the beginning to 6 months after the last cell infusion (women of childbearing age include premenopausal women and postmenopausal women)
• Women within 2 years).
• \. Subject must sign and date written informed consent.

You may not qualify if:

• Pregnant and lactating women.
• Known history of human immunodeficiency virus (HIV) infection; Acute or chronic active hepatitis B (HBsAg positive);
• Acute or chronic active hepatitis C (positive for HCV antibody). Syphilis antibody positive; Epstein-barr virus DNA quantification
• copies; Cytomegalovirus (CMV) infection (IgM positive).
• \. Severe infection that is in the active stage or clinically poorly controlled.
• \. Existing heart disease requiring treatment or hypertension determined to be poorly controlled by the investigator (defined as standardized blood pressure reduction)
• Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure \> 90 mmHg after treatment).
• \. Presence of any of the following cardiac clinical symptoms or diseases:
• A) Unstable angina pectoris;
• B) Myocardial infarction occurred within 1 year;
• C) Resting state ecg QTc \> 450ms(male) or QTc \> 470ms (female);
• D) Abnormalities of clinical significance (such as heart rate, conduction, morphological characteristics, etc.) detected by resting ecg examination
• Complete left bundle branch block or grade 3 heart block or grade 2 heart block or PR interval \>
• ms;
• E) There are factors that increase the risk of prolonged QTc and abnormal heart rate, such as heart failure, hypokalemia, and congenital long QT

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

NK Cell Lectin-Like Receptor Subfamily K; Automobiles; Cell Count

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Receptors, NK Cell Lectin-Like; Receptors, Natural Killer Cell; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Motor Vehicles; Transportation; Technology, Industry, and Agriculture; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cell Physiological Phenomena

Study Officials

• Weijia Fang, MD

  The First Affiliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weijia Fang, MD

CONTACT

13758211655; weijiafang@zju.edu.cn

zheng hong

CONTACT

18050102049

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 25, 2021
• First Posted: January 28, 2022
• Study Start: December 10, 2021
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)