A Single-center, Open-label, Single-arm Clinical Study of the Safety and Efficacy of KD-496 CAR-T Therapy in Advanced NKG2DL+/CLDN18.2+ Solid Tumors

jianming xu1 site in 1 country18 target enrollmentOctober 13, 2022

ConditionsGastric Cancer Pancreatic Cancer Solid Tumor

Overview

Phase: Early Phase 1
Intervention: Not specified
Conditions: Gastric Cancer
Sponsor: jianming xu
Enrollment: 18
Locations: 1
Primary Endpoint: Dose-limiting toxicity (DLT) rate
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

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.

Registry

clinicaltrials.gov

Start Date

October 13, 2022

End Date

June 1, 2026

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

jianming xu

Responsible Party

Sponsor Investigator

Principal Investigator

jianming xu

Leading Site Principal Investigator

The Affiliated Hospital of the Chinese Academy of Military Medical Sciences

Eligibility Criteria

Inclusion Criteria

•Patients diagnosed as advanced solid tumors histopathologically or cytologically, such as gastric cancer and pancreatic cancer.
•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);
•Age 18-75 years;
•ECOG score 0-1;
•Expected survival ≥ 3 months;
•Patients must meet coagulation parameters and have adequate peripheral venous access for apheresis, and must also have enough PBMC to manufacture CAR T cells;
•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;
•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);

Exclusion Criteria

•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.
•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.

Outcomes

Primary Outcomes

Dose-limiting toxicity (DLT) rate

Time Frame: 3 months after single infusion

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

treatment-emergent adverse events(TEAEs)

Time Frame: 3 months after single infusion

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

CAR positive T cells in patients

Time Frame: 6 months after single infusion

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

Secondary Outcomes

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)