NKG2D CAR-T(KD-025) in the Treatment of Advanced NKG2DL+ Solid Tumors

Launched by CANCER INSTITUTE AND HOSPITAL, CHINESE ACADEMY OF MEDICAL SCIENCES · Jul 14, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment called NKG2D CAR-T cell therapy for patients with advanced solid tumors, such as ovarian, cholangiocarcinoma, and colorectal cancer. The goal is to find out if this therapy is safe and effective for people who have already tried standard treatments without success or cannot tolerate those treatments. To participate, patients need to be between 18 and 70 years old, have a specific type of tumor that tests positive for NKG2DL, and meet certain health criteria.

If you or a loved one is interested in this trial, you can expect to receive an infusion of specially modified T cells designed to target your cancer. Participants will be closely monitored for any side effects and overall health during the study. It's important to note that there are specific health conditions that may disqualify someone from joining, such as active infections or certain heart and lung issues. Additionally, participants will need to agree to use contraception during the study and for some time afterward, to ensure safety during treatment.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • 1. Patients diagnosed as advanced solid tumors histopathologically or cytologically, such as ovarian, cholangiocarcinoma, and colorectal 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 18-70 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 (according to the positive comprehensive score of 0-12 points, positive SCORE of NKG2DL ≥2) positive confirmed byImmunohistochemistry. Biopsy tissue must be no more than 1 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 ≤2ULN; Serum alanine amino transferase (ALT) or aspartate aminotransferase (AST)≤2.5ULN (≤2.5 times with liver metastasis); 3) Creatinine ≤1.5ULN or eGFR≥ 60mL /min/1.73m\^2 \[eGFR=186×(age)-0.203×SCr-1.154(mg/dl), eGFR timing in women was 0.742\]; 4) International normalized ratio (INR) or prothrombin time (PT) ≤1.5ULN; 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. Patients fully understand the test and voluntarily sign the informed consent;
• • 11. Patient agree to use approved contraceptive methods (e.g., birth control pills, barrier devices, iuds, contraindicated drugs) during the study and for at least 12 months after last cell infusion, until no CAR-T cells were detected by two consecutive PCR tests.
• Exclusion Criteria:
• • 1. Patients had received any gene therapy (including CAR-T cell therapy) or any T cell therapy, Active bacteria or viral or fungal infection and not controlled after anti-infective treatment (positive blood test 72 hours before infusion), Syphilis, 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 have an autoimmune disease or organ transplant, require chronic systemic steroid therapy or any other form of immunosuppressive drugs;
• • 3. A history of serious heart or lung disease, including uncontrolled hypertension medication, and any condition that occurred within the past 6 months: congestive heart failure (New York Heart Association functional classification ≥3), cardiac angioplasty and stents, myocardial infarction, unstable angina, or other clinically severe heart disease;
• • 4. Detected clinically relevant central nervous system (CNS) metastases and/or pathologies, such as seizures, cerebral ischemia/bleeding, dementia, cerebellar diseases or autoimmune diseases affecting the CNS;
• • 5. The Patients' history or existing evidence of any condition such as neuroticism, psychosis, immunology, metabolism, and infectious disease, in any treatment, or laboratory abnormalities may confuse the outcome of the study, interfere with the Patients' participation during the study, or not participate in the Patients' best interests with investigator treatment;
• • 6. The Patients have a history of hematologic malignancy or concurrent history of other malignant primary solid tumors, except for: 1) Patients with cervical or breast cancer in situ who have no evidence of disease for more than 3 years after radical treatment; 2) Patients who have successfully received definite resection of tumor in situ and have no evidence of disease for ≥5 years;
• • 7. Received chemotherapy, radiation, small molecule, biologic cancer therapy, immunotherapy, or other experimental drugs within 4 weeks prior to study initiation,
• • 8. Pregnant or lactating women;
• • 9. The investigator considers the Patients have or with current historical evidence of any condition, therapy, or laboratory anomaly that may confound the results of the study, interfere with the Patients' participation in the fulltime study and the requirements of the cooperative trial, not controlled medical, psychological, family, social, or geographic conditions, or not participate.