Advanced Solid Cancers
Conditions
Brief summary
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Targeted Activated DC combined with CAR-T therapy in patients with Advanced Solid Cancers.This combination therapy activates dendritic cells (DCs) to precisely target the tumor site, reshaping the tumor immune microenvironment, breaking down the immunosuppressive barrier, and allowing CAR-T cells to penetrate deeper into the tumor more efficiently, precisely and persistently killing cancer cells.
Interventions
BIOLOGICALTargeted Activated Dendritic Cells
Autologous dendritic cells (DCs) genetically modified to express chimeric antigen receptor (CAR) and activation domain
BIOLOGICALTargeted CAR-T Cells
Autologous T cells genetically modified to express chimeric antigen receptor (CAR)
Sponsors
Hainan Cancer Hospital
Frontiergate Biopharm（Hainan） Co., LTD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years and ≤ 75 years, regardless of gender; 2. Advanced solid tumors with clear pathological confirmation, including but not limited to gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, etc.; at least one measurable lesion meeting RECIST 1.1 criteria (according to RECIST 1.1, the longest diameter of a measurable lesion on spiral CT scan ≥ 10 mm, or the short diameter of a pathological lymph node ≥ 15 mm); 3. Tumor tissue positive for Claudin 18.2, GCC, TROP2, or PSMA targets by immunohistochemistry (IHC) (expression intensity ≥ 2+; percentage of positive cells ≥ 40%); 4. Meets the indications for PBMC collection and has no contraindications for cell collection; 5. Failure of standard second-line treatment, or lack of a standard treatment regimen; or refusal to receive chemotherapy (with signed documentation); 6. ECOG performance status: 0-1; 7. Life expectancy: ≥ 3 months; 8. Toxicities from prior chemotherapy or other anti-tumor therapies must have resolved after a washout period (except for residual alopecia), ensuring that all organ functions meet the inclusion criteria; 9. Adequate organ function, including: 1. Adequate immune function: absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L, monocyte count ≥ 0.1 × 10⁹/L. 2. Adequate hematopoietic function: platelet count ≥ 75 × 10⁹/L, hemoglobin ≥ 90 g/L. Patients must not have received blood transfusions or treatments such as granulocyte colony-stimulating factor, thrombopoietin, or erythropoietin within 14 days prior to the blood count assessment. 3. Adequate liver function: total bilirubin (TBIL) \< 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 × ULN. 4. Adequate renal function: creatinine (Cr) ≤ 1.5 × ULN. 5. Adequate coagulation function: prothrombin time (PT) or activated partial thromboplastin time (APTT) \< 1.5 × ULN, and international normalized ratio (INR) \< 1.5. 10. Individuals of childbearing potential must agree to use effective contraception during the study; 11. Ability to understand and willingness to sign a written informed consent form; 12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Exclusion criteria
1. Oncological emergencies requiring immediate intervention, such as malignant pericardial effusion or tamponade, superior vena cava syndrome, or spinal cord compression; 2. Significant cardiovascular disease, including: 1. Documented major cardiovascular events within the past 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or prior angioplasty, stent implantation, or coronary artery bypass grafting; 2. Clinically significant QT interval prolongation (QTcF \> 470 ms for women or QTcF \> 450 ms for men); 3. Clinically significant bleeding tendency or coagulation disorders (e.g., hemophilia); 4. Active infection with HIV, syphilis, hepatitis B virus (HBV), or hepatitis C virus (HCV); 5. History of involuntary commitment due to mental illness, or any psychiatric condition deemed by the investigator to make the patient unsuitable for the trial; 6. Concurrent autoimmune diseases, or long-term use of immunosuppressants or systemic corticosteroids; 7. Poor compliance, as assessed by the investigator; 8. Prior treatment with any targeted CAR-T cell therapy within 3 months before this CAR-T infusion; 9. Uncontrolled active bacterial or fungal infections; 10. Any other condition that, in the opinion of the investigator, makes the patient ineligible for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | 2 years post cell infusion | To evaluate adverse events following infusion of targeted activated dendritic cells (DC) and CAR-T cells, with an assessment of the incidence and severity of treatment-related toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematological abnormalities, infections, autoimmune reactions, and secondary malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 2 years | The percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1 |
| Disease Control Rate (DCR) | 2 years | The percentage of participants who achieved Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1 |
| Progression-free survival (PFS) | 2 years | PFS is defined as the time from the date of cell infusion until the date of tumor progression or death from any cause |
| Changes in the Immune Microenvironment | 1 month post cell infusion | Assess the changes in the tumor immune microenvironment (TIME) following combined therapy with targeted activated dendritic cells (DCs) and CAR-T cells. The analysis will focus on the composition, density, and functional status of key immune cell populations, including T cell subsets (e.g., CD4+, CD8+), B cells, DC subsets, tumor-associated macrophages (TAMs), and regulatory T cells (Tregs). |
Countries
China
Contacts
CONTACTHAIFENG LIN
PRINCIPAL_INVESTIGATORHAIFENG LIN
Hainan Cancer Hospital
Outcome results
None listed