Treatment for advanced colorectal cancer using targeted CAR-T and CAR-DC therapies

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

This study is testing a new combination treatment using special immune cells to see if it can help people with advanced colorectal cancer live longer and feel better.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (other)
• Drugs / interventions: chemotherapy, immunotherapy, CAR-T
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06946615 on ClinicalTrials.gov

What this trial studies

This clinical study aims to evaluate the safety and preliminary efficacy of a combination therapy involving Claudin18.2-targeted CAR-T cells and CAR-DCs in patients with advanced colorectal cancer. It is an open-label, single-arm study that will assess the maximum tolerated dose of the therapy during a dose-escalation phase. Additionally, the study will measure overall response rates, overall survival, and disease-free survival, while also evaluating the persistence and functional activity of the infused cells.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced colorectal cancer who have confirmed Claudin18.2 expression and have experienced disease progression after standard treatments.

Not a fit: Patients who do not express Claudin18.2 in their tumor tissue or have not progressed after standard treatments 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 colorectal cancer who have not responded to standard therapies.

How similar studies have performed: While the approach of using CAR-T and CAR-DC therapies is innovative, similar studies have shown promise in other cancers, suggesting potential for success in this context.

Eligibility criteria

Inclusion Criteria:

1. Participants must have a histologically or cytologically confirmed diagnosis of colonic or rectal adenocarcinoma, 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).
2. Claudin18.2 expression must be confirmed as positive in tumor tissue by immunohistochemistry (IHC).
3. Disease progression following standard treatments, including prior administration of fluoropyrimidines, irinotecan, and oxaliplatin. Disease progression may occur during or after treatment. Prior molecular targeted therapies are allowed.
4. ECOG performance status of 0 to 1.
5. Expected survival of at least 6 months.
6. Toxicities related to prior antitumor treatments must have resolved to baseline or ≤ Grade 1 (except for residual alopecia); peripheral neurotoxicity ≤ Grade 2 is acceptable. The minimum washout period is 4 weeks for chemotherapy and immunotherapy, and 2 weeks for targeted therapy.
7. Adequate organ function, defined as follows:

   * Hematologic function: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count ≥ 75 × 10\^9/L, and hemoglobin ≥ 9 g/dL. No blood transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), or erythropoietin (EPO) allowed within 14 days prior to hematology testing.
   * Hepatic function: Total bilirubin (TBIL) \< 1.5 × upper limit of normal (ULN); AST and ALT \< 2.5 × ULN. For patients with Gilbert's syndrome, TBIL \< 2 × ULN. For patients with liver metastases, AST and ALT must be \< 5 × ULN.
   * Renal function: Serum creatinine ≤ 1.5 × ULN; or if \> 1.5 × ULN, creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockcroft-Gault formula.
   * Coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) \< 1.5 × ULN; international normalized ratio (INR) \< 1.5 or within the therapeutic range if on anticoagulation therapy.
8. Participants of childbearing potential must agree to use effective contraception during the study period.
9. Participants must have adequate comprehension and voluntarily sign the informed consent form.
10. Willingness to comply with all study-related procedures, including scheduled visits, drug administration, laboratory assessments, and other protocol requirements.

Exclusion Criteria:

1. Tumor-related emergencies requiring immediate intervention, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
2. Clinically significant cardiovascular disease, including:

   * Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmias, or history of angioplasty, stent implantation, or coronary artery bypass grafting (CABG);
   * Prolonged QT/QTcF interval with clinical significance (QT/QTcF \> 470 ms in females or \> 450 ms in males).
3. Clinically significant bleeding disorders or coagulopathies, such as hemophilia.
4. Active infections including HIV, syphilis, or active hepatitis B or C:

   * Hepatitis B: HBV-DNA ≥ 1000 IU/mL;
   * Hepatitis C: Positive HCV RNA with abnormal liver function.
5. History of involuntary psychiatric hospitalization due to mental illness or other psychiatric disorders deemed unsuitable for treatment by the investigator.
6. Presence of autoimmune diseases or chronic use of immunosuppressive agents or corticosteroids.
7. Poor medication compliance or inability to adhere to the treatment protocol.
8. Any other condition that, in the opinion of the investigator, warrants exclusion from the study.

Where this trial is running

Hangzhou, Zhejiang

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Principal investigator: Ying Yuan — Second Affiliated Hospital, School of Medicine, Zhejiang University
• Study coordinator: Ying Yuan

Conditions: Colorectal Neoplasia, Chimeric Antigen Receptor Dendritic Cells, Chimeric Antigen Receptor T-Cells, Colorectal Neoplasms