Clinical trial NCT06010862: Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors
Official title: A Safety and Efficacy Clinical Study of CEA-targeted CAR-T Therapy forCEA-positive Advanced/Metastatic Malignant Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastric Cancer
Colon Cancer
Pancreas Cancer
Esophagus Cancer
Cholangiocarcinoma
Lung Cancer
Breast Cancer
Keywords: CAR-T
CEA
Lead sponsor: Chongqing Precision Biotech Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: The First Affiliated Hospital of Nanchang University
First posted: 2023-08-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase I clinical study to evaluate the safety and tolerability of CAR-T in patients with CEA-positive advanced/metastatic solid tumors, and to obtain the maximum tolerated dose of CAR-T and phase II Recommended dose.

Detailed description: This is a single-center, double-arm, open-label study. The study plans to set up 2 groups,Intravenous infusion group have 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CEA-positive advanced/metastatic solid tumors.Intraperitoneal injection group have 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CD70-positive advanced/metastatic solid tumors.

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 failure (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 positive rate ≥ 10%), the serum CEA of the patient is required to 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\>3.0×10\^9/L, neutrophils\>0.8×10\^9/L, lymphocytes cells\>0.5×10\^9/L, platelets\>75×10\^9/L, hemoglobin\>80g/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 patients with liver tumor infiltration, it can be relaxed to ≤5.0×ULN);
   5. Total bilirubin≤3.0×ULN;
   6. Oxygen saturation ≥95% 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. Those who have central nervous system metastasis or meningeal metastasis at the time of screening are judged by the investigator to be unsuitable for inclusion;
2. Participated in other clinical studies within 1 month before screening;
3. vaccinated with live attenuated vaccine within 4 weeks before screening;
4. 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);
5. Active infection or uncontrollable infection requiring systemic treatment;
6. Patients with intestinal obstruction, active gastrointestinal bleeding, or a history of gastrointestinal bleeding within 3 months;
7. Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumor therapy has not improved to the baseline level or ≤ grade 1;
8. 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 a history of unexplained syncope (except those caused by vasovagal or dehydration);
   4. History of severe non-ischemic cardiomyopathy;
9. Patients with active autoimmune disease, or other patients requiring long-term immunosuppressive therapy;
10. 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;
11. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer test 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;
12. Women who are pregnant or breastfeeding;
13. Other investigators deem it unsuitable to participate in the research.

Primary outcomes:
measure: Incidence of Adverse events after CEA CAR-T cells infusion [Safety and Tolerability]
timeFrame: 28 days
measure: Obtain the maximum tolerated dose of CEA CAR-T cells[Safety and Tolerability]
timeFrame: 28 days
Secondary outcomes:
measure: Disease control rate of CAR-T cell preparations in CEA positive advanced malignancies [Effectiveness]
timeFrame: 3 months
measure: Objective response rate (ORR) of CEA CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
timeFrame: 3 months
measure: Duration of Response (DOR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
timeFrame: 3 months
measure: Overall survival(OS)of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
timeFrame: 2 years
measure: Progress-free survival(PFS) of CEA CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
timeFrame: 2 years
measure: AUCS of CEA CAR-T cells [Cell dynamics]
timeFrame: 3 months
measure: CMAX of CEA CAR-T cells [Cell dynamics]
timeFrame: 3 months
measure: TMAX of CEA CAR-T cells[Cell dynamics]
timeFrame: 3 months
measure: Pharmacodynamics of CEA CAR-T cells[Cell dynamics]
timeFrame: 3 months
Other outcomes:
measure: The correlation between CEA positive rate and safety
timeFrame: 2 years
measure: Correlation between CEA positive rate and efficacy
timeFrame: 2 years
measure: Overall survival(OS)of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
timeFrame: 2 years
measure: Progress-free survival(PFS) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
timeFrame: 2 years
measure: Duration of Response (DOR) of CEA CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]
timeFrame: 2 years
Locations:
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
Study officials:
affiliation: The First Affiliated Hospital of Nanchang University
name: Fei Li, M.D
role: PRINCIPAL_INVESTIGATOR
References: