Study of CEA Targeting CAR-T in the Treatment of CEA-Positive Advanced Malignant Solid Tumors

Launched by WEIJIA FANG, MD · Feb 8, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called CAR-T therapy, which uses specially modified immune cells to target and fight certain types of advanced cancers that are positive for a protein called carcinoembryonic antigen (CEA). The trial focuses on patients with cancers like colorectal, stomach, esophageal, and pancreatic cancer that have not responded to standard treatments. It's currently in its early Phase I stage, which means researchers are primarily looking to see if this treatment is safe and to determine the right dosage.

To be eligible for the trial, participants need to be at least 18 years old and have advanced cancer that has not improved after at least two prior treatments. They should have a recent test showing their cancer cells are CEA-positive and meet specific health requirements. If someone joins the trial, they will receive the CAR-T therapy and be closely monitored for safety and effectiveness. It's important for participants to understand that this is experimental, and while it may help, it may not work for everyone. Additionally, all participants must agree to use effective birth control during the study and for a year afterward.

Gender

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Eligibility criteria

• Inclusion Criteria:
• Subjects must meet all the following criteria to be eligible for the study:
• • 1. Age≥18 years, regardless of gender.
• • 2. Diagnosed with advanced, metastatic, or recurrent malignant tumors confirmed by histology or pathology, primarily including colorectal cancer, esophageal cancer, gastric cancer, pancreatic cancer, lung cancer, or cholangiocarcinoma.
• • 3. Failure of at least second-line standard therapy (due to disease progression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or a lack of effective treatment options.
• • 4. Immunohistochemical staining of tumor samples within 3 months confirming CEA positivity (distinct membrane staining with a positivity rate of≥10%); if the immunohistochemical result of the tumor sample is more than 3 months old at the time of screening (distinct membrane staining with a positivity rate of≥10%), the patient's serum CEA must exceed 10µg/L.
• • 5. At least one evaluable lesion according to RECIST 1.1 criteria.
• • 6. ECOG score of 0-2 (Appendix 2).
• • 7. No severe psychiatric disorders.
• 8. Unless specifically stated otherwise, subjects' major organ functions must meet the following conditions:
• • 1. Blood routine: WBC\>2.0×109/L, neutrophils\>0.8×109/L, lymphocytes\>0.5×109/L, platelets\>50×109/L, hemoglobin\>90g/L;
• • 2. Cardiac function: Echocardiography indicating a left ventricular ejection fraction≥50%, and no significant abnormalities on electrocardiogram;
• • 3. Renal function: Serum creatinine≤2.0×ULN;
• • 4. Liver function: ALT and AST ≤3.0×ULN (may be relaxed to≤5.0×ULN if liver tumor infiltration is present);
• • 5. Total bilirubin≤2.0×ULN;
• • 6. Oxygen saturation\>92% without supplemental oxygen. 9. Eligible for apheresis or venous blood collection, with no contraindications for cell collection.
• • 10. Subjects agree to use reliable and effective contraceptive methods from signing the informed consent form until 1 year after receiving CAR-T cell infusion (excluding natural family planning methods).
• • 11. The patient or their guardian agree to participate in this clinical trial and signs the ICF, indicating an understanding of the trial's purpose and procedures and willingness to participate.
• Exclusion Criteria:
• Subjects meeting any of the following criteria will be excluded from the study:
• • 1. Clinically symptomatic central nervous system or leptomeningeal metastasis at the time of screening, or other evidence suggesting that central nervous system or leptomeningeal metastases are not controlled, as judged unsuitable for inclusion by the investigator.
• • 2. Participation in another clinical study within 1 month prior to screening.
• • 3. Receipt of live attenuated vaccines within 4 weeks prior to screening.
• • 4. Receipt of the following anti-tumor treatments before screening: Chemotherapy, targeted therapy, or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter).
• • 5. Presence of active or uncontrolled infections requiring systemic treatment.
• • 6. Patients with intestinal obstruction, active gastrointestinal bleeding, a history of major gastrointestinal bleeding within 3 months, severe gastroduodenal ulcers, or severe gastrointestinal inflammation such as ulcerative colitis.
• • 7. Toxicity from previous anti-tumor therapy that has not improved to baseline levels or≤Grade 1, except for alopecia or peripheral neuropathy.
• 8. Presence of any of the following cardiac conditions:
• • 1. New York Heart Association (NYHA) Stage III or IV congestive heart failure;
• • 2. Myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to enrollment;
• • 3. Clinically significant ventricular arrhythmia or history of unexplained syncope (excluding vasovagal or dehydration-related causes);
• • 4. History of severe non-ischemic cardiomyopathy.
• • 9. Presence of active autoimmune diseases or other conditions requiring long-term immunosuppressive therapy.
• • 10. Diagnosis of another untreated malignancy within the past 3 years, except for in situ cervical cancer or basal cell carcinoma of the skin.
• • 11. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA levels exceeding the normal range; positive for hepatitis C virus (HCV) antibodies with peripheral blood HCV RNA levels exceeding the normal range; positive for human immunodeficiency virus (HIV) antibodies; or positive syphilis test.
• • 12. Pregnant or breastfeeding women.
• • 13. Any other conditions deemed unsuitable for participation in the study by the investigator.