CEA-targeted CAR-T therapy for advanced malignant tumors

A Safety and Efficacy Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced Malignant Solid Tumors

This study is testing a new CAR-T cell therapy that targets a specific protein in advanced solid tumors like colorectal and pancreatic cancers to see if it can help patients feel better and improve their treatment outcomes.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (industry)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT05415475 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of CAR-T cell therapy targeting carcinoembryonic antigen (CEA) in patients with advanced malignant solid tumors, including colorectal, esophageal, stomach, and pancreatic cancers. It is an open-label, single-arm study that aims to determine the recommended dose and infusion scheme for CEA-positive tumors. The trial builds on previous findings that CAR-T cells can effectively kill CEA-positive tumor cells without serious adverse events. The study will optimize CAR structure and culture methods to enhance the therapeutic potential of the CAR-T cell preparations.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced, metastatic, or recurrent CEA-positive malignant tumors who have failed at least second-line standard treatments.

Not a fit: Patients with tumors that do not express CEA or those who have not undergone prior 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 CEA-positive solid tumors that have not responded to standard therapies.

How similar studies have performed: Previous studies targeting CEA with CAR-T therapy have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Advanced, metastatic or recurrent malignant tumors diagnosed by histology or pathology, mainly colorectal cancer, esophageal cancer, gastric cancer, and pancreatic cancer;
3. After receiving at least second-line standard treatment and failing (disease progression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack of effective treatment methods;
4. Immunohistochemical staining of tumor samples within 3 months confirmed that the tumor was CEA positive (clear membrane staining, positive rate ≥ 10%); the patient's serum CEA should exceed 10ug/L.
5. At least one assessable lesion according to RECIST 1.1 criteria;
6. ECOG score 0-2 points;
7. No serious mental disorder;
8. Unless otherwise specified, the function of the vital organs of the subject shall meet the following conditions:

   1. Blood routine: white blood cells\>2.0×109/L, neutrophils\>0.8×109/L, lymphocytes cells\>0.5×109/L, platelets\>50×109/L, hemoglobin\>90g/L;
   2. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
   3. Renal function: serum creatinine≤2.0×ULN;
   4. Liver function: ALT and AST ≤3.0×ULN (for those with liver tumor infiltration, it can be relaxed to≤5.0×ULN);
   5. Total bilirubin≤2.0×ULN;
   6. Oxygen saturation \> 92% in non-oxygen state.
9. Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;
10. Subjects agree to use reliable and effective contraceptive methods for contraception within 1 year after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);
11. The patients themselves or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.

Exclusion Criteria:

1. Previous CAR-T therapy or other gene-modified cell therapy；
2. CNS metastases or meningeal metastases with clinical symptoms at the time of screening, or there is other evidence that the patient's central nervous system metastases or meningeal metastases have not been controlled, and are judged by the investigator to be unsuitable for inclusion;
3. Participated in other clinical studies within 1 month before screening;
4. vaccinated with live attenuated vaccine within 4 weeks before screening;
5. Received the following anti-tumor treatments before screening: Received chemotherapy, targeted therapy or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter);
6. Active infection or uncontrollable infection requiring systemic treatment;
7. Patients with intestinal obstruction, active gastrointestinal bleeding, or a history of gastrointestinal bleeding within 3 months;
8. Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumor therapy has not improved to the baseline level or ≤ grade 1;
9. Suffering from any of the following heart diseases:

   1. New York Heart Association (NYHA) stage III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
   3. Clinically significant ventricular arrhythmia, or history of syncope of unknown origin (caused by vasovagal except those caused by neurosis or dehydration);
   4. History of severe non-ischemic cardiomyopathy;
10. Patients with active autoimmune disease, or other patients requiring long-term immunosuppressive therapy;
11. Suffering from other uncured malignant tumors in the past 3 years or at the same time, except cervical carcinoma in situ and basal cell carcinoma of the skin;
12. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV) RNA test is greater than the normal range; human immunodeficiency virus (HIV) antibody positive; syphilis test positive;
13. Women who are pregnant or breastfeeding;
14. Other investigators deem it unsuitable to participate in the study.

Where this trial is running

Jinan, Shandong

• Shandong Second Provincial General Hospital — Jinan, Shandong, China (RECRUITING)

Study contacts

• Principal investigator: Jingwang Bi, M.D — Shandong Second Provincial General Hospital
• Study coordinator: Jingwang Bi, M.D

Conditions: Colorectal Cancer, Esophageal Cancer, Stomach Cancer, Pancreatic Cancer, Metastatic Tumor, Recurrent Cancer, CAR-T, CEA