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

NCT05396300 | Recruiting Phase 1

• 1 other identifier: PBC039
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Cancers; Gastric Cancer; Colorectal Cancer

Keywords

CAR-T; CEA; CEA-positive advanced malignant solid tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Disease control rate of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]

  3 months

• Changes in serum tumor markers of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]

  3 months

• AUCS of CEA-CAR-T cells [Cell dynamics]

  1 years

• CMAX of CEA-CAR-T cells [Cell dynamics]

  1 years

• TMAX of CEA-CAR-T cells[Cell dynamics]

  1 years

Other Outcomes (7)

• Objective response rate (ORR) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]

  1 years

• Duration of Response (DOR) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]

  1 years

• Progress-free survival(PFS) of CEA- CAR-T treatment in patients with CEA-positive advanced malignancies[Effectiveness]

  1 years

Study Arms (3)

Intraperitoneal infusion of FAST CEA-targeted CAR-T

EXPERIMENTAL

Intraperitoneal infusion of FAST CEA-targeted CAR-T cells by 4 dose levels

Biological: Intraperitoneal infusion of FAST CEA-targeted CAR-T

Intravenous of CEA-targeted CAR-T

EXPERIMENTAL

Infusion of CEA-targeted CAR-T cells by dose of 3-10x106 cells/kg

Biological: CEA CAR-T cells

intraperitoneal injection of CEA-targeted CAR-T

EXPERIMENTAL

Infusion of CEA-targeted CAR-T cells by dose of 3-10x106 cells/kg

Biological: CEA CAR-T cells

Interventions

CEA CAR-T cells BIOLOGICAL

Administration method: intravenous infusion or intraperitoneal injection； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

Intravenous of CEA-targeted CAR-T

Intraperitoneal infusion of FAST CEA-targeted CAR-T BIOLOGICAL

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.

Intraperitoneal infusion of FAST CEA-targeted CAR-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, male or female;
• Advanced, metastatic or recurrent malignant tumors diagnosed by histology or pathology, mainly colorectal cancer;
• 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;
• 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.
• At least one assessable lesion according to RECIST 1.1 criteria;
• ECOG score 0-2 points;
• No serious mental disorder;
• Unless otherwise specified, the function of the vital organs of the subject shall meet the following conditions:
• 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;
• Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
• Renal function: serum creatinine≤2.0×ULN;
• Liver function: ALT and AST ≤3.0×ULN (for those with liver tumor infiltration, it can be relaxed to≤5.0×ULN);
• Total bilirubin≤2.0×ULN;
• Oxygen saturation \> 92% in non-oxygen state.
• Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;

You may not qualify if:

• Participated in other clinical studies within 1 month before screening;
• vaccinated with live attenuated vaccine within 4 weeks before screening;
• 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);
• Active infection or uncontrollable infection requiring systemic treatment;
• Patients with intestinal obstruction, active gastrointestinal bleeding, or a history of gastrointestinal bleeding within 3 months;
• Except for alopecia or peripheral neuropathy, the toxicity of previous anti-tumor therapy has not improved to the baseline level or ≤ grade 1;
• Suffering from any of the following heart diseases:
• New York Heart Association (NYHA) stage III or IV congestive heart failure;
• Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
• Clinically significant ventricular arrhythmia, or history of syncope of unknown origin (caused by vasovagal except those caused by neurosis or dehydration);
• History of severe non-ischemic cardiomyopathy;
• Patients with active autoimmune disease, or other patients requiring long-term immunosuppressive therapy;
• 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;
• 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;
• Women who are pregnant or breastfeeding;

Sponsors & Collaborators

• Weijia Fang, MD: lead
• Chongqing Precision Biotech Co., Ltd: collaborator

Study Sites (1)

First affiliated hospital, Zhejiang University

Hangzhou, Zhejiang, 310006, China

RECRUITING

Related Publications (2)

• 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.

  PMID: 41760800 DERIVED

• 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.

  PMID: 39734708 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Study Officials

• Weijia Fang, M.D

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weijia Fang, M.D

CONTACT

13758211655; weijiafang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: May 31, 2022
• Study Start: May 25, 2022
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Locations

CN (1)