Claudin18.2-targeted activated dendritic cell plus CAR-T therapy for advanced pancreatic cancer

Exploratory Clinical Study of Combined Claudin18.2-Targeted Activated DC and CAR-T Therapy in Patients With Advanced Pancreatic Cancer

This trial will test whether combining Claudin18.2-targeted activated dendritic cells with Claudin18.2 CAR-T cells helps people with advanced pancreatic cancer whose tumors express Claudin18.2.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Hainan Cancer Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Haikou, Hainan)
• Trial ID: NCT07416240 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm early-phase 1 trial combines Claudin18.2-targeted activated dendritic cells with Claudin18.2-specific CAR-T cells to test safety and early signs of benefit in advanced pancreatic cancer. The approach uses patient-derived PBMCs to produce activated DCs intended to reshape the tumor immune microenvironment and CAR-T cells that target Claudin18.2-positive tumor cells. Eligible participants must have histologically confirmed advanced pancreatic cancer, measurable disease by RECIST v1.1, and tumor Claudin18.2 expression of ≥2+ in ≥50% of cells. The study is conducted at Hainan Cancer Hospital and includes monitoring for adverse events, tumor response, and immune biomarkers.

Who should consider this trial

Good fit: Adults aged 18–80 with histologically confirmed advanced pancreatic cancer, measurable disease, tumor Claudin18.2 expression ≥2+ in ≥50% of cells, ECOG 0–1, able to undergo PBMC collection, and who have exhausted or declined standard second-line options are eligible.

Not a fit: Patients whose tumors are negative for Claudin18.2, who have ECOG >1, a life expectancy under three months, or unresolved toxicities from prior treatments are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, this combination could improve tumor control by enabling CAR-T cells to penetrate and kill Claudin18.2-positive pancreatic tumors more effectively.

How similar studies have performed: Claudin18.2-targeted therapies including CAR-T have shown early promising signals in other tumor types but CAR-T success in solid tumors is still limited, so this combination approach remains relatively novel and unproven.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years, upper limit ≤ 80 years, gender not limited;
2. Participants must have a histologically or cytologically confirmed diagnosis of advanced pancreatic cancer, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm).
3. Tumor tissue positive for Claudin 18.2 by immunohistochemical detection (expression intensity ≥ 2+; expression range ≥ 50%);
4. Meeting the indications for PBMC collection and having no other contraindications for cell collection;
5. Failure of standard second-line treatment or lack of a standard treatment regimen; or signing a refusal to undergo chemotherapy.
6. ECOG score: 0-1;
7. Life expectancy: ≥ 3 months;
8. Toxic reactions from previous chemotherapy and other anti-tumor treatments must be resolved through a washout period (except for residual hair loss), ensuring that all functional parameters meet the inclusion criteria;
9. Sufficient organ function, including:

   1. Sufficient immune function, i.e., absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L, monocyte count ≥ 0.1 × 10⁹/L.
   2. Sufficient hematopoietic function, i.e., 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 complete blood count examination. c) Sufficient liver function, i.e., total bilirubin (TBIL) \< 2 × upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 × ULN.

   d) Sufficient kidney function, i.e., creatinine (Cr) ≤ 1.5 × ULN. e) Sufficient coagulation function, i.e., prothrombin time (PT) or activated partial thromboplastin time (APTT) \< 1.5 × ULN, and international normalized ratio (INR) \< 1.5.
10. Individuals of fertility must be willing to use contraception;
11. Sufficient understanding and willingness to sign an informed consent form;
12. Willingness to comply with visit schedules, medication plans, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Emergency oncological conditions requiring immediate treatment, such as malignant pericardial effusion or tamponade, superior vena cava obstruction syndrome, spinal cord compression, etc.
2. Significant cardiovascular disease, such as:

   1. • A confirmed cardiovascular event within the past 6 months, such as myocardial infarction, angina pectoris, heart failure, severe arrhythmia, or previous angioplasty, stent implantation, or coronary artery bypass grafting;
   2. • Clinically significant QT interval prolongation (QTcF \> 470ms for women or QTcF \> 450ms for men).
3. Clinically significant bleeding tendency or coagulation disorders, such as hemophilia;
4. HIV infection, syphilis infection, hepatitis B infection, or hepatitis C infection.
5. History of involuntary custody due to mental illness or other mental illness deemed unsuitable for treatment by the treating physician;
6. Accompanied by other autoimmune diseases, or long-term use of immunosuppressants or steroids;
7. Poor patient compliance as assessed by the investigator;
8. Previous treatment with any target CAR-T within 3 months prior to this CAR-T treatment;
9. Uncontrollable active bacterial or fungal infections;
10. Other conditions deemed necessary to be ruled out by the physician.

Where this trial is running

Haikou, Hainan

• Hainan Cancer Hospital — Haikou, Hainan, China (Recruiting)

Study contacts

• Principal investigator: Haifeng Lin — Hainan Cancer Hospital
• Study coordinator: Haifeng Lin

Conditions Advanced Pancreatic Cancer