Using Anti-CEA CAR-T Cells to Treat Liver Metastases from Colorectal Cancer

A Clinical Study to Evaluate the Safety and Efficacy of Anti-CEA CAR-T Cells in the Treatment of Postoperative Minimal Residual Lesions in Colorectal Cancer Patients With Liver Metastases

This study is testing a new treatment using special immune cells to see if it can help patients with colorectal cancer who have had surgery but still have tiny traces of cancer in their liver.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changhai Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, Chimeric Antigen Receptor, Immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05240950 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of Anti-CEA CAR-T cells to target and treat liver metastases in patients with colorectal cancer. The approach focuses on patients who have undergone radical surgery for their primary colorectal cancer and have no measurable disease, yet still show signs of minimal residual disease through circulating tumor DNA. The study aims to evaluate the safety and effectiveness of this innovative immunotherapy in a Phase 1 setting, potentially addressing a significant gap in treatment for solid tumors. By targeting carcinoembryonic antigen (CEA), which is often elevated in gastrointestinal tumors, the trial seeks to improve outcomes for patients at risk of recurrence.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 who have undergone R0 resection for liver metastases from colorectal cancer and have detectable CEA expression.

Not a fit: Patients with measurable disease or those who do not express CEA in their tumors may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of recurrence in colorectal cancer patients with liver metastases.

How similar studies have performed: While CAR-T cell therapy has shown success in hematological cancers, its application in solid tumors like colorectal cancer is still emerging and largely untested.

Eligibility criteria

Inclusion Criteria:

1. ≥18 years old, ≤75 years old, male or female;
2. Patients diagnosed with liver metastasis of colorectal cancer underwent radical surgery for the primary lesion of colorectal cancer, and R0 resection was performed for the liver metastasis (R0 resection was required for other organ metastasis). There was no measurable disease or tumor remnants (except invisible or unmeasurable disease) were found by imaging examination after surgery;
3. Patients with CEA expression detected by immunohistochemistry in primary tumor and liver metastasis tumor tissues (CEA expression detected by pathology was more than 50%);
4. Life expectancy ≥6 months;
5. Performance status (PS) score 0-2, Karnofsky performance status (KPS) score above 60;
6. Patients with ctDNA MRD still positive or positive again after adjuvant chemotherapy (including preoperative neoadjuvant chemotherapy);
7. Important organ functions are sufficient, such as New York Heart Association (NYHA) heart function grade III or above, hemoglobin ≥90g/L, hypoxia; Liver function: total bilirubin ≤1.5×ULN (total bilirubin ≤3×ULN in liver metastasis), ALT≤2.5×ULN, AST≤2.5×ULN (ALT or/and AST≤5×ULN in liver metastasis); Renal function: serum creatinine ≤1.5×ULN and creatinine clearance rate ≥50 mL/min. The creatinine clearance rate was only calculated when serum creatinine ≤1.5×ULN. Minimum reserve of lung function (dyspnea no higher than grade 1 and oxygen saturation \> 91% without oxygen);
8. Sufficient mononuclear cells (PBMC) can be obtained from peripheral veins without contraindications;
9. Patients of childbearing age had no birth plan within 1 year after cell infusion and took effective contraceptive measures.

Exclusion Criteria:

1. Have a history of severe central nervous system diseases;
2. Residual disease or tumor remnants can be seen in imaging, or tumor lesions cannot be resected in other tissues or organs;
3. The presence of serious non-malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
4. Prior treatment with CAR-T or other gene-modified T cells;
5. Participated in other clinical studies within 30 days prior to screening or plan to participate in other clinical studies during the study period;
6. Patients with active Hepatitis B (HBV-DNA copy number \>105copies/ml), active Hepatitis C (HCV-RNA copy number \>ULN), HIV infection, treponema pallidum infection at screening time;
7. The existence of uncontrollable systemic infectious diseases;
8. Other multiple malignant tumors in addition to colorectal cancer and its metastasis;
9. Chinese herbal medicine, systemic glucocorticoids or other immunosuppressants may be required within 2 weeks prior to enrollment or during the trial period, which may negatively affect lymphocyte activity or number;
10. Pregnancy and lactation;
11. The existence of severe gastroduodenal ulcer, severe ulcerative colitis and other serious intestinal inflammation;
12. The existence of serious respiratory diseases;
13. Those who cannot provide enough white tablets for tumor pathology for next-generation sequencing (NGS) detection (at least 3 white tablets are expected);
14. The investigator judged that there were other conditions that were not suitable for the clinical study.

Where this trial is running

Shanghai, Shanghai Municipality

• Department of Colorectal Surgery in Changhai Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Conditions Colorectal Cancer; Metastatic Liver Cancer; colorectal cancer; liver metastasis; CAR-T cell; minimal residue disease