NKG2D/CLDN18.2 CAR-T(KD-496) in the Treatment of Advanced NKG2DL+/CLDN18.2+ Solid Tumors

NCT05583201 | Recruiting Early Phase 1

• 1 other identifier: KD-496-XJM
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Cancer; Pancreatic Cancer; Solid Tumor

Keywords

NKG2D; CLDN18.2

Outcome Measures

Primary Outcomes (3)

• treatment-emergent adverse events(TEAEs)

  An adverse event is any undesirable experience associated with the use of a medical product in a patient

  3 months after single infusion

• Dose-limiting toxicity (DLT) rate

  A drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.

  3 months after single infusion

• CAR positive T cells in patients

  The time of CAR-T cell reach the peak and turn back to baseline

  6 months after single infusion

Secondary Outcomes (3)

• Objective response rate(ORR)

  1 month, 2 month, 3 month, 6 month, 1 year after cell infusion

• Progression free survival(PFS)

  1 month, 2 month, 3 month, 6 month, 1 year after cell infusion

• Complete remission (CR)

  1 month, 2 month, 3 month, 6 month, 1 year after cell infusion

Study Arms (1)

KD-496 cell infusion

EXPERIMENTAL

Each subject will receive KD-496 cell infusion

Biological: KD-496

Interventions

KD-496 BIOLOGICAL

Autologous genetically modified anti-NKG2DL/CLDN18.2 CAR transduced T cells

KD-496 cell infusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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:
• 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);
• 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);
• Creatinine ≤1.5ULN or eGFR≥60mL /min（Cockcroft and Gault）
• International normalized ratio (INR) ≤1.2;
• Lung function: ≤ grade 1 dyspnea(according to NCI-CTCAE V5.0), SaO2≥91%;
• 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.
• 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.

You may not qualify if:

• 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)；
• Patients had received any gene therapy (including CAR-T cell therapy) or any T cell therapy；
• Patients had participated in other drug trials within 4 weeks prior to the study；
• 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；
• Patients with sudden pulmonary disease, interstitial lung disease, pulmonary fibrosis, acute pulmonary disease, etc;
• 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:
• )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.
• \. Clinically symptomatic brain metastases with the exception of patients with stable, asymptomatic brain metastases treated with radiotherapy or surgery for 14 days.
• \. 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.
• 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.
• Prior to apheresis, he received the following antitumor treatments:
• Cytotoxic treatment within 14 days;
• 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;
• Treatment with monoclonal antibodies within 21 days;
• Immunomodulator therapy within 7 days;

Sponsors & Collaborators

• jianming xu: lead
• KAEDI: collaborator

Study Sites (1)

Chinese PLA General Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Leading Site Principal Investigator

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 17, 2022
• Study Start: October 13, 2022
• Primary Completion: June 1, 2024
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)