Exploratory Clinical Study of Targeted Activated DC and CAR-T Therapy in Advanced Solid Cancers

Official title

Exploratory Clinical Study of Targeted Activated DC and CAR-T Therapy in Patients With Advanced Solid Cancers.

Overview

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

• Biological Targeted Activated Dendritic Cells
  Autologous dendritic cells (DCs) genetically modified to express chimeric antigen receptor (CAR) and activation domain
• Biological Targeted CAR-T Cells
  Autologous T cells genetically modified to express chimeric antigen receptor (CAR)

Primary outcome measures

• Adverse Events (AEs) [Time frame: 2 years post cell infusion]

Secondary outcome measures (4)

• Objective Response Rate (ORR) [Time frame: 2 years]
• Disease Control Rate (DCR) [Time frame: 2 years]
• Progression-free survival (PFS) [Time frame: 2 years]
• Changes in the Immune Microenvironment [Time frame: 1 month post cell infusion]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years and ≤ 75 years, regardless of gender;
• 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);
• Tumor tissue positive for Claudin 18.2, GCC, TROP2, or PSMA targets by immunohistochemistry (IHC) (expression intensity ≥ 2+; percentage of positive cells ≥ 40%);
• Meets the indications for PBMC collection and has no contraindications for cell collection;
• Failure of standard second-line treatment, or lack of a standard treatment regimen; or refusal to receive chemotherapy (with signed documentation);
• ECOG performance status: 0-1;
• Life expectancy: ≥ 3 months;
• 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;
• Adequate organ function, including:

• 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.
• 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.
• Adequate liver function: total bilirubin (TBIL) < 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN.
• Adequate renal function: creatinine (Cr) ≤ 1.5 × ULN.
• Adequate coagulation function: prothrombin time (PT) or activated partial thromboplastin time (APTT) < 1.5 × ULN, and international normalized ratio (INR) < 1.5.
• Individuals of childbearing potential must agree to use effective contraception during the study;
• Ability to understand and willingness to sign a written informed consent form;
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion criteria

• Oncological emergencies requiring immediate intervention, such as malignant pericardial effusion or tamponade, superior vena cava syndrome, or spinal cord compression;
• Significant cardiovascular disease, including:

• 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;
• Clinically significant QT interval prolongation (QTcF > 470 ms for women or QTcF > 450 ms for men);
• Clinically significant bleeding tendency or coagulation disorders (e.g., hemophilia);
• Active infection with HIV, syphilis, hepatitis B virus (HBV), or hepatitis C virus (HCV);
• History of involuntary commitment due to mental illness, or any psychiatric condition deemed by the investigator to make the patient unsuitable for the trial;
• Concurrent autoimmune diseases, or long-term use of immunosuppressants or systemic corticosteroids;
• Poor compliance, as assessed by the investigator;
• Prior treatment with any targeted CAR-T cell therapy within 3 months before this CAR-T infusion;
• Uncontrolled active bacterial or fungal infections;
• Any other condition that, in the opinion of the investigator, makes the patient ineligible for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Hainan Cancer Hospital — Haikou

Identifiers

NCT: NCT07475182 · EC-2025-041-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗