A Clinical Study of CEA-targeted CAR-T in the Treatment of CEA-positive Advanced Malignant Solid Tumors

A Phase I Clinical Study of Anti-CEA CAR-T Therapy in the Treatment of CEA-positive Advanced Malignant Solid Tumors

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

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Solid Cancers
• Intervention / Treatment: Biological: CEA CAR-T cells; Biological: Intraperitoneal infusion of FAST CEA-targeted CAR-T

Detailed Description

This is a single-center, open-label, dose-escalation study consisting of three distinct treatment cohorts for patients with CEA-positive advanced malignant solid tumors:

Cohort 1 (Intravenous infusion): A dose-escalating (3+3 design) study with 4 dose levels,: 1.0×106, 3.0×106, 5.0×106 CAR+ cells/kg and 7.0×106 CAR+ cells/kg.

Cohort 2 (Intraperitoneal injection): A dose-escalating (3+3 design) study with 3 dose levels：1.0×106, 3.0×106,and 5.0×106 CAR+ cells/kg.

Cohort 3 (FAST CAR-T Intraperitoneal infusion): A dose-escalating study (3+3 design) with 4 dose levels: 2.0×10⁵, 3.0×10⁵, 4.0×10⁵, and 5.0×10⁵ CAR+ cells/kg.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Weijia Fang, M.D; Phone Number: 13758211655; Email: weijiafang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Recruiting
      • First affiliated hospital, Zhejiang University
      • Contact: Weijia fang, MD; Phone Number: 13758211655; Email: weijia.fang@163.com
      • Principal Investigator: Weijia fang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;
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%); If over 3 months, 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. 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;
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 history of syncope of unknown origin (caused by vasovagal except those caused by neurosis 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 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 study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous of CEA-targeted CAR-T; Infusion of CEA-targeted CAR-T cells by dose of 3-10x106 cells/kg	Biological: CEA CAR-T cells; Administration method: intravenous infusion or intraperitoneal injection； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.
Experimental: intraperitoneal injection of CEA-targeted CAR-T; Infusion of CEA-targeted CAR-T cells by dose of 3-10x106 cells/kg	Biological: CEA CAR-T cells; Administration method: intravenous infusion or intraperitoneal injection； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.
Experimental: Intraperitoneal infusion of FAST CEA-targeted CAR-T; Intraperitoneal infusion of FAST CEA-targeted CAR-T cells by 4 dose levels	Biological: Intraperitoneal infusion of FAST CEA-targeted CAR-T; Intraperitoneal infusion of FAST CEA-targeted CAR-T (PTC13); Subjects will be treated with Fludarabine and Cyclophosphamide based lymphodepleting chemotherapy before CAR-T cell infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse events after CEA-CAR-T cells infusion [Safety and Tolerability]	Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)	28 days
Obtain the maximum tolerated dose of CEA-CAR-T cells[Safety and Tolerability]	Dose-limiting toxicity after cell infusion	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]	Disease control rate: including CR, PR and SD	3 months
Changes in serum tumor markers of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]	Changes in serum tumor markers：CEA、 CA199、 CA125	3 months
AUCS of CEA-CAR-T cells [Cell dynamics]	AUCS is defined as the area under the curve in 28 days and 90 days	1 years
CMAX of CEA-CAR-T cells [Cell dynamics]	CMAX is defined as the highest concentration of CEA-CAR-T cells expanded in peripheral blood	1 years
TMAX of CEA-CAR-T cells[Cell dynamics]	TMAX is defined as the time to reach the highest concentration	1 years
Pharmacodynamics of CEA-CAR-T cells[Cell dynamics]	The content of free CEA in peripheral blood at each time point measured by Chemiluminescence immunoassay	1 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]	Objective response rate includes：CR、PR	1 years
Duration of Response (DOR) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]	DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause	1 years
Progress-free survival(PFS) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]	PFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression.	1 years
Overall survival(OS)of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]	OS will be assessed from the first CEA-CAR-T cell infusion to death from any cause	1 years
Proportion of tumor cells in tumor tissue of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies	The rate of tumor cell in tumor tissue will be measured by biopsy and immunohistochemistry	1 years
Changes in the number of tumor-infiltrating immune cells of CEA- CAR-T treatment in patients with CEA-positive	the number of tumor-infiltrating immune cells will be measured by biopsy and immunohistochemistry	1 years
CEA expression level of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies	The CEA expression in tumor tissue will be measured by biopsy and immunohistochemistry	1 years

Collaborators and Investigators

• Sponsor: Weijia Fang, MD
• Collaborators: Chongqing Precision Biotech Co., Ltd
• Investigators: Principal Investigator: Weijia Fang, M.D, First Affiliated Hospital of Zhejiang University

Publications and helpful links

General Publications

• Gao Y, Li J, Zhang H, Zhang Y, Qian S, Zhu X, Hong L, Xie L, Fu Q, Bao X, Tong Z, Li Y, Li B, Wang L, Shen J, Zhang Q, He X, Zheng Y, Yao C, Liu L, Zhao P, Campos PV, Yang Z, Qian C, Fang W. Hypoxia-responsive CEA-targeted CAR T cells in CEA-positive solid tumors through intraperitoneal or intravenous infusion: a phase 1 trial. Nat Cancer. 2026 Feb 27. doi: 10.1038/s43018-026-01124-3. Online ahead of print.
• Ye K, Yu C, Shen Z. Severe refractory colitis after intraperitoneal infusion of CEA-directed CAR T cells in patients with colorectal cancer. Ther Adv Med Oncol. 2024 Dec 23;16:17588359241309825. doi: 10.1177/17588359241309825. eCollection 2024.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: May 25, 2022
• First Submitted That Met QC Criteria: May 25, 2022
• First Posted (Actual): May 31, 2022

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; CEA; CEA-positive advanced malignant solid tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Stomach Neoplasms; Colorectal Neoplasms
• Other Study ID Numbers: PBC039

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No