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

NCT06946615 | Recruiting Phase 1

• 1 other identifier: 2024-0255
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2-targeted CAR-DC combined with CAR-T cell therapy in patients with advanced colorectal cancer.

Conditions

Colorectal Neoplasia

Keywords

Chimeric Antigen Receptor Dendritic Cells; Chimeric Antigen Receptor T-Cells; Colorectal Neoplasms

Outcome Measures

Primary Outcomes (2)

• Safety: Incidence and severity of adverse events

  To evaluate adverse events occurring within the first three months following infusion of Claudin18.2-targeted CAR-T cells and CAR-DCs. The assessment includes incidence and severity of treatment-related symptoms such as neurological toxicity, hematological abnormalities, infections, autoimmune reactions, and secondary malignancies.

  First 3 month post CAR-T cells and CAR-DCs infusion

• Efficacy: Remission Rate

  To evaluate the proportion of participants who achieve an objective tumor response, including complete remission (CR) and partial remission (PR)

  3 months post CAR-T cells and CAR-DCs infusion

Secondary Outcomes (7)

• Progression-Free Survival

  Up to 24 months post CAR-T cells and CAR-DCs infusion

• Overall Survival

  Up to 24 months post CAR-T cells and CAR-DCs infusion

• Relapse Rate

  Up to 24 months post CAR-T cells and CAR-DCs infusion

• Duration of Response

  Up to 24 months post CAR-T cells and CAR-DCs infusion

• In Vivo Persistence of CAR-T cells and CAR-DCs and Cytokine Profile Monitoring

  First 2 weeks post CAR-T cells and CAR-DCs infusion

Study Arms (1)

CAR-T and CAR-DC Combination Therapy

EXPERIMENTAL

This arm involves the sequential administration of two biological interventions, with Claudin18.2-targeted CAR-DCs administered first, followed by Claudin18.2-targeted CAR-T cells.

Biological: Claudin18.2-targeted CAR-T Cells; Biological: Claudin18.2-targeted CAR-DCs

Interventions

Claudin18.2-targeted CAR-T Cells BIOLOGICAL

Autologous T cells genetically modified to express a chimeric antigen receptor (CAR) targeting Claudin18.2.

CAR-T and CAR-DC Combination Therapy

Claudin18.2-targeted CAR-DCs BIOLOGICAL

Autologous dendritic cells (DCs) genetically modified to express a chimeric antigen receptor (CAR) targeting Claudin18.2.

CAR-T and CAR-DC Combination Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Claudin18.2 expression must be confirmed as positive in tumor tissue by immunohistochemistry (IHC).
• 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.
• ECOG performance status of 0 to 1.
• Expected survival of at least 6 months.
• 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.
• 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.
• Participants of childbearing potential must agree to use effective contraception during the study period.
• Participants must have adequate comprehension and voluntarily sign the informed consent form.
• Willingness to comply with all study-related procedures, including scheduled visits, drug administration, laboratory assessments, and other protocol requirements.

You may not qualify if:

• Tumor-related emergencies requiring immediate intervention, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
• 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).
• Clinically significant bleeding disorders or coagulopathies, such as hemophilia.
• 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.
• History of involuntary psychiatric hospitalization due to mental illness or other psychiatric disorders deemed unsuitable for treatment by the investigator.
• Presence of autoimmune diseases or chronic use of immunosuppressive agents or corticosteroids.
• Poor medication compliance or inability to adhere to the treatment protocol.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Ying Yuan

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Yuan

CONTACT

+86-13858193601; yuanying1999@zju.edu.cn

Shanshan Weng

CONTACT

+86-13758118823; 2310053@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2025
• First Posted: April 27, 2025
• Study Start: April 8, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

CN (1)