Using modified T cells to treat metastatic colorectal cancer

A Clinical Study on the Safety and Efficacy of GCC Targeting CAR-T Cells (WD-01) for Metastatic Colorectal Cancer

This study is testing a new treatment using modified immune cells to see if it can help people with advanced colorectal cancer by targeting specific cancer cells.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Wondercel Biotech (ShenZhen) (Industry-sponsored)
• Drugs / interventions: tocilizumab, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Hefei, Anhui and 1 other locations)
• Trial ID: NCT06675513 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of an autologous CAR-T therapy, known as WD-01, targeting GCC in patients with metastatic colorectal cancer. Participants will undergo a pre-conditioning chemotherapy regimen before receiving modified T cells that are designed to recognize and attack cancer cells expressing the GCC antigen. The study aims to determine the maximum tolerated dose, assess dose-limiting toxicities, and measure treatment efficacy through objective response rates and progression-free survival. Data will be collected on both short-term and long-term outcomes following treatment.

Who should consider this trial

Good fit: Ideal candidates include patients with pathologically confirmed metastatic colorectal cancer who have failed second-line treatment and exhibit GCC expression in their tumors.

Not a fit: Patients with colorectal cancer that does not express GCC or those who are not eligible due to poor organ function or performance status may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option for patients with metastatic colorectal cancer who have exhausted other treatment avenues.

How similar studies have performed: While CAR-T therapies have shown success in hematological malignancies, this specific approach targeting metastatic colorectal cancer is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Pathologically confirmed colorectal cancer. Immunohistochemistry (IHC) assessment shows GCC expression in tumor lesions of ≥1+ in an average of over 40% of the area (evaluated by randomly selecting at least five tumor regions).

Patients with metastatic colorectal cancer who have failed second-line treatment.

At least one measurable extracranial lesion per RECIST version 1.1 criteria. Expected survival of ≥90 days.

Normal function of major organs, meeting the following criteria:

1. ECOG performance status of 0-1 or KPS score \>70.
2. Hematology parameters meeting: Hemoglobin (HB) ≥80 g/L, Absolute Neutrophil Count (ANC) ≥1.5 × 10\^9/L, Platelets (PLT) ≥80 × 10\^9/L, Lymphocytes (LY) ≥0.5 × 10\^9/L.
3. Biochemistry parameters meeting: Total Bilirubin (TBIL) ≤2.0 × ULN (upper limit of normal); ALT and AST ≤2.5 × ULN; Serum Creatinine (Cr) ≤1 × ULN, Creatinine Clearance Rate \>40 mL/min (by Cockcroft-Gault formula).
4. Left ventricular ejection fraction \>55%. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and agree to use appropriate contraception during the study and for 8 weeks after the last CAR-T administration (women who have undergone sterilization or have been postmenopausal for at least 2 years are considered not of childbearing potential).

Voluntary participation in the study, with signed informed consent, good compliance, and willingness to cooperate with follow-up.

Exclusion Criteria:

* Pregnant or lactating women. Receipt of small molecule chemotherapy, targeted agents, other investigational drugs, or monoclonal antibodies within 14 days prior to cell collection for enrollment.

Participation in other clinical trials within 4 weeks prior to the start of this study.

Uncontrolled hypertension that cannot be adequately managed with a single antihypertensive drug (systolic BP \>160 mmHg, diastolic BP \>100 mmHg), myocardial ischemia or infarction of grade ≥1, arrhythmia of grade ≥1 (including QT interval ≥440 ms), or cardiac insufficiency.

Long-standing, unhealed wounds or fractures. History of substance abuse that cannot be discontinued or a history of psychiatric disorders.

Severe intestinal adhesions, bowel obstruction, or conditions that may cause bowel perforation or abdominal wall fistula after treatment.

Uncontrolled or active fungal, bacterial, viral, or other infections. Grade ≥2 hematologic toxicity or grade ≥3 non-hematologic toxicity at enrollment as per NCI-CTCAE version 5.0 criteria.

Known HIV infection or active hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) infection.

Presence of indwelling catheters or drainage tubes (e.g., biliary drainage tubes or thoracic/abdominal drainage tubes or pericardial catheters). Use of specialized central venous catheters is permitted.

Severe malnutrition (for patients \<70 years, BMI \<18.5 kg/m\^2; for patients ≥70 years, BMI \<20 kg/m\^2).

History of severe allergic reactions to key therapeutic agents in this study (including fludarabine, cyclophosphamide, mesna, tocilizumab, and anti-infective drugs used during preconditioning).

History of disseminated intravascular coagulation (DIC), deep vein thrombosis, or pulmonary embolism within 6 months prior to enrollment.

History of autoimmune diseases that cause terminal organ damage or require systemic immunosuppressive/systemic disease-modifying drugs within 2 years prior to enrollment (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).

Any disease that may interfere with the safety or efficacy assessment of the study treatment.

Female participants who are unwilling to use contraception from the time of consent until 6 months after completing CAR-T cell infusion.

Where this trial is running

Hefei, Anhui and 1 other locations

• Anhui Provincial Cancer Hospital — Hefei, Anhui, China (Recruiting)
• Huazhong University of Science and Technology Union Hospital (Nanshan Hospital) — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Clinical Deveopment Director

Conditions CRC; Metastatic Colorectal Cancer; Autologous CAR-T therapy; WD-01; Wondercel