Trial Title:
NKG2D/CLDN18.2 CAR-T(KD-496) in the Treatment of Advanced NKG2DL+/CLDN18.2+ Solid Tumors
NCT ID:
NCT05583201
Condition:
Gastric Cancer
Pancreatic Cancer
Solid Tumor
Conditions: Keywords:
NKG2D
CLDN18.2
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
KD-496
Description:
Autologous genetically modified anti-NKG2DL/CLDN18.2 CAR transduced T cells
Arm group label:
KD-496 cell infusion
Summary:
This is a Phase 1, single-arm, single-center, open-label study to evaluate the safety and
effectiveness of NKG2D/CLDN18.2-based CAR-T cells infusion in the treatment of advanced
NKG2DL+/CLDN18.2+ solid tumors.
Detailed description:
This is an open-label, dose escalation/expansion study to assess the safety,tolerability,
and efficacy of KD-496 cell infusion in patients with advanced NKG2DL+/CLDN18.2+ solid
tumors. In this study, the enrollment of the patients must meet the inclusion and
exclusion criteria. All subjects will be undergo screening, pre-treatment (cell product
preparation, lymphodepleting chemotherapy), treatment and follow up.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients diagnosed as advanced solid tumors histopathologically or cytologically,
such as gastric cancer and pancreatic cancer. 2. Patients fail standard treatment ,
or cannot tolerate standard treatment, or there is no standard treatment, the
standard treatment recommendations refer to the latest version of the guidelines of
the national comprehensive cancer network (NCCN) or the guidelines of the Chinese
society of Clinical Oncology (CSCO); 3. Age 18-75 years; 4. ECOG score 0-1; 5.
Expected survival ≥ 3 months; 6. Patients must meet coagulation parameters and have
adequate peripheral venous access for apheresis, and must also have enough PBMC to
manufacture CAR T cells; 7. NKG2DL/CLDN18.2 (according to the positive comprehensive
score of 0-12 points, positive SCORE of NKG2DL and CLDN18.2 ≥5) positive confirmed
by Immunohistochemistry. Biopsy tissue must be no more than 2 year, if not, must
obtain new tissue material from a recent surgical or diagnostic biopsy; 8. Eligible
organ and bone marrow functions defined as follows:
1. Absolute neutrophil count ≥1.5×10^9/L, lymphocyte count ≥0.5×10^9/ L, platelet count
≥90×10^9/L, hemoglobin ≥90g/L (no blood transfusion or Erythropoietin within 7
days);
2. Total bilirubin ≤1.5ULN; (Patients with Gilbert syndrome were diagnosed with total
bilirubin ≤3mg/dL) Serum alanineamino transferase (ALT) or aspartate
aminotransferase(AST)≤3ULN(ALT and AST in patients with liver metastases ≤5ULN);
3. Creatinine ≤1.5ULN or eGFR≥60mL /min（Cockcroft and Gault）
4. International normalized ratio (INR) ≤1.2;
5. Lung function: ≤ grade 1 dyspnea(according to NCI-CTCAE V5.0), SaO2≥91%;
6. Cardiac function:
Cardiac ejection fraction (LVEF) detected by echocardiography or MUGA ≥50% 1 month before
enrollment. 9. Patients must have measurable lesions as defined by RECIST 1.1; 10. If the
patient is HBsAg positive or HBcAb positive, HBV-DNA should be < 2000IU/ml. HBsAg
positive patients.Antiviral therapy must be received according to the Chronic Hepatitis B
Prevention and Treatment Guidelines 2019.
11.Patients fully understand the test and voluntarily sign the informed consent; 12.
Patient agree to use approved contraceptive methods (e.g., birth control pills, barrier
devices, iuds, contraindicated drugs) during the study and for at least 13 months after
last cell infusion, until no CAR-T cells were detected by two consecutive PCR tests.
Exclusion Criteria:
1. Human immunodeficiency virus (HIV), Active hepatitis B (HBV DNA≥500IU/ml) or
hepatitis c (anti-HCV positive and HCV RNA higher than the detection limit of
analysis method)；
2. Patients had received any gene therapy (including CAR-T cell therapy) or any T cell
therapy；
3. Patients had participated in other drug trials within 4 weeks prior to the study；
4. Patients with history or CT examination revealed active tuberculosis infection
within 1 year before enrollment or patients diagnosed with active pulmonary
tuberculosis 1 year ago without regular treatment；
5. Patients with sudden pulmonary disease, interstitial lung disease, pulmonary
fibrosis, acute pulmonary disease, etc;
6. Subjects with pre-existing or active autoimmune diseases, or those with potential
for recurrence (e.g., Wolf erythematosus systemic) Sores, rheumatoid arthritis,
inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis,
vasculitis, kidneyGlomerulonephritis, etc.), or patients at high risk (such as those
who have received organ transplants and require immunosuppressive therapy). But
allowSubjects with the following diseases were enrolled:
1)Type 1 diabetic patients with stable disease after a fixed dose of insulin; 2)Only
autoimmune hypothyroidism on hormone replacement therapy 3)Skin conditions that do not
require systemic treatment (e.g., eczema, a rash of up to 10% of the body surface, silver
flakes without ophthalmic symptoms Disease,etc.); 4)The use of immunosuppressants, such
as steroids, should be phased out before the study begins if the patient has adrenal
glands.If they are not functional, corticosteroids can be continued to replace the
physiological dose (dose equivalent to ≤10 mg prednisone/day) 7.A history of severe heart
disease, including medically poorly controlled hypertension (systolic blood pressure
>160mmHg and/or diastolic blood pressure) Pressure >90mmHg), and any of the following
conditions occurring within the past 6 months: patients with QT prolongation syndrome,
screening,Phase 12 lead ECG results QTc interval >470mSEC, congestive heart failure (New
York Heart Association grade ≥Class Ⅲ), cardiac angioplasty and stenting, myocardial
infarction, unstable angina pectoris, severe arrhythmia or the researcher assessed heart
disease that was not eligible for enrollment.
8. Clinically symptomatic brain metastases with the exception of patients with stable,
asymptomatic brain metastases treated with radiotherapy or surgery for 14 days.
9. Other central nervous system disorders judged by the investigators to be likely to
affect the trial: such as epilepsy/seizures, cerebral ischemia/hemorrhage, Dementia,
cerebellar disease or autoimmune disease affecting the central nervous system.
10.Complicating hematologic malignancy or other primary malignant solid tumors, except in
the following cases: 1) Patients with cervical or breast cancer accepted radical therapy
without evidence of disease for more than 3 years; 2) The orthotopic tumor was
successfully removed without definite resection patients with ≥5 years of evidence of
disease.
11.Prior to apheresis, he received the following antitumor treatments:
1. Cytotoxic treatment within 14 days;
2. have received small molecule targeted therapy within 14 days or at least 5
half-lives, whichever is shorter,Therapy or investigational drug therapy, or
treatment with invasive investigational medical devices;
3. Treatment with monoclonal antibodies within 21 days;
4. Immunomodulator therapy within 7 days;
5. Radiotherapy within 14 days. 12. Female subjects who are pregnant or breastfeeding
during the screening period; 13. With a history of severe hypersensitivity to the
primary therapeutic agents used in this study included fludarabine,
cyclophosphamide, and PROPHYlaxis during pretreatment Tocilizumab and anti-infective
drugs for CRS) 14.Untreated brain metastases or symptoms of brain metastases.
15.Patients with heart disease or poorly controlled high blood pressure who need
treatment.
16.Patients with unstable or active peptic ulcers or gastrointestinal bleeding.
17.Patients who have a history of organ transplantation or are preparing for organ
transplantation.
18.Patients requiring anticoagulant therapy (e.g., warfarin or heparin). 19.Patients
requiring long-term antiplatelet therapy (aspirin,dose>300mg/d;clopidogrel,dose>75mg/d)
20.Patients had undergone major surgery or serious injury 4 weeks before the start of the
study, or would undergo major surgery during the study.
21.Toxicity > grade 1 from previous antineoplastic therapy before screening (except
alopecia).
22.Conditions that other researchers deemed inappropriate for inclusion
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese PLA General Hospital
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
jianming Xu
Phone:
13910866712
Email:
jianmingxu2014@163.com
Start date:
October 13, 2022
Completion date:
June 1, 2026
Lead sponsor:
Agency:
jianming xu
Agency class:
Other
Collaborator:
Agency:
KAEDI
Agency class:
Other
Source:
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05583201
