NKG2D CAR-T therapy for advanced solid tumors

A Single-center, Open, Single-arm Clinical Study of the Safety and Efficacy of KD-025 CAR-T Therapy in Advanced NKG2DL+ Solid Tumors

This study is testing a new CAR-T cell therapy called KD-025 to see if it can safely help people with advanced solid tumors that have a specific marker.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: CAR T, CAR-T, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06509490 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of KD-025, a type of CAR-T cell therapy, in patients with advanced solid tumors that express NKG2DL. It is an open-label, single-arm study where participants will undergo screening, lymphodepleting chemotherapy, and then receive the CAR-T cell infusion. The study aims to assess the tolerability and efficacy of this treatment approach in a specific patient population. Participants will be closely monitored throughout the treatment and follow-up phases.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-70 with advanced NKG2DL+ solid tumors who have failed standard treatments or cannot tolerate them.

Not a fit: Patients with solid tumors that do not express NKG2DL or those who are not eligible based on the study's inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with advanced solid tumors that currently have limited or no effective therapies.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this specific approach targeting NKG2DL+ solid tumors is relatively novel and has not been extensively tested in previous studies.

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.

Where this trial is running

Beijing, Beijing Municipality

• Cancer hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Ning Li, MD — Nccicams
• Study coordinator: Ning Li, MD

Conditions Safety Issues