CEA-Targeted CAR-T Therapy in CEA-Positive Advanced Solid Tumors

Clinical Study of CEA-Targeted Chimeric Antigen Receptor T Lymphocytes (CAR-T) in Advanced CEA-Positive Malignant Solid Tumors

This study is a single-arm, open-label, dose-escalating + dose-expansion clinical study, aiming to evaluate the safety and efficacy of CEA-targeted CAR-T cell preparations, and to preliminarily observe the study drug in CEA-positive advanced malignant tumors. The pharmacokinetic characteristics of CAR-T cell preparations for the treatment of patients with CEA-positive advanced malignancies were obtained and the recommended dose and infusion schedule.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Esophageal Cancer; Lung Cancer; Rectal Cancer; Colon Cancer; Pancreas Cancer
• Intervention / Treatment: Biological: CEA-targeted CAR-T cells; Biological: CEA-targeted CAR-T cells; Biological: CEA-targeted CAR-T cells

Detailed Description

According to the different infusion methods, patients will be assigned to three parallel subgroups: intravenous infusion, intrapleural infusion, and intraperitoneal infusion.

Within each subgroup, the study is conducted in two sequential parts:

1. .Part A (dose-escalation): escalation begins at the lowest dose level; 3-6 subjects are enrolled at each dose level;
2. .Part B (dose-expansion): additional subjects are treated at the recommended dose identified in Part A to further evaluate safety and preliminary efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Donglai Lv, MD; Phone Number: +86 13655600090; Email: lvxunhuan@163.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230031
      • Recruiting
      • The 901 Hospital of Joint Logistics Support Force of People Liberation Army
      • Principal Investigator: Donglai Lv, MD
      • Contact: Donglai Lv, MD; Phone Number: +86 13655600090; Email: lvxunhuan@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years, no gender restriction;
2. Histopathologically confirmed diagnosis of advanced, metastatic, or recurrent malignant tumors, primarily including colorectal cancer, esophageal cancer, gastric cancer, pancreatic cancer, lung cancer, and cholangiocarcinoma;
3. Failure of at least second-line standard treatment (disease progression or intolerance, such as surgery, chemotherapy, radiotherapy, etc.) or lack of effective treatment options;
4. Immunohistochemical staining of tumor samples showing CEA positivity (clear membrane staining, positivity rate ≥ 10%) within the past 3 months; if the immunohistochemical result is older than 3 months (clear membrane staining, positivity rate ≥ 10%), serum CEA must exceed 10 µg/L;
5. At least one evaluable lesion according to RECIST 1.1 criteria;
6. ECOG performance status of 0-2;
7. Expected survival of ≥ 12 weeks;
8. No severe psychiatric disorders;

9. Unless otherwise specified, the following important organ function criteria must be met:

   1. Hematology: White blood cells > 2.0 × 10^9/L, neutrophils > 0.8 × 10^9/L, lymphocytes > 0.5 × 10^9/L, platelets > 50 × 10^9/L, hemoglobin > 90 g/L;
   2. Cardiac function: Echocardiogram shows ejection fraction ≥ 50%, ECG shows no significant abnormalities;
   3. Renal function: Serum creatinine ≤ 2.0 × ULN;
   4. Liver function: ALT and AST ≤ 3.0 × ULN (can be relaxed to ≤ 5.0 × ULN for patients with liver tumor infiltration);
   5. Total bilirubin ≤ 2.0 × ULN;
   6. Oxygen saturation > 92% without supplemental oxygen;
10. Eligible for single or venous blood collection, and no contraindications for cell collection;
11. The subject agrees to use reliable and effective contraception methods from the time of signing the informed consent form until 1 year after CAR-T cell infusion (excluding rhythm method);
12. The subject or their authorized guardian agrees to participate in this clinical trial and signs the informed consent form (ICF), indicating understanding of the trial's purpose and procedures and willingness to participate in the study.

Exclusion Criteria:

1. Clinically symptomatic central nervous system metastasis or meningeal metastasis at screening, or other evidence indicating that central nervous system or meningeal metastasis has not been controlled, as determined by the investigator, making the patient unsuitable for enrollment.
2. Participation in another clinical trial within 1 month prior to screening.
3. Receipt of live attenuated vaccines within 4 weeks prior to screening.
4. Received the following anti-tumor treatments within 14 days or at least 5 half-lives (whichever is shorter) prior to screening: chemotherapy, targeted therapy, or other experimental drug treatments.
5. Active infection requiring systemic treatment or an uncontrolled infection.
6. Bowel obstruction, active gastrointestinal bleeding, or a history of major gastrointestinal bleeding within the last 3 months, or severe gastrointestinal conditions such as severe gastric or duodenal ulcers, severe ulcerative colitis, or other severe gastrointestinal inflammations.
7. Toxicity from prior anti-tumor treatments has not improved to baseline levels or ≤ grade 1, except for alopecia or peripheral neuropathy.

8. Any of the following cardiac conditions:

   1. New York Heart Association (NYHA) Class 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 arrhythmias, or history of unexplained syncope (excluding cases due to vasovagal or dehydration);
   4. Severe non-ischemic cardiomyopathy.
9. Active autoimmune diseases or other conditions requiring long-term use of immunosuppressive therapy.
10. History of another malignancy within the past 3 years, excluding treated and stable 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 above the normal range; positive for hepatitis C virus (HCV) antibodies with peripheral blood HCV RNA levels above the normal range; positive for HIV antibodies; or positive for syphilis testing.
12. Pregnant or breastfeeding women.
13. Any other conditions that, in the opinion of the investigator, make the patient unsuitable for participation 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 1-15x10^5 cells/kg	Biological: CEA-targeted CAR-T cells; Administration method: intravenous infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.; Biological: CEA-targeted CAR-T cells; Administration method: intrapleural infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.; Biological: CEA-targeted CAR-T cells; Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
Experimental: Intrapleural infusion of CEA-targeted CAR-T; Infusion of CEA-targeted CAR-T cells by dose of 1-15x10^5 cells/kg	Biological: CEA-targeted CAR-T cells; Administration method: intravenous infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.; Biological: CEA-targeted CAR-T cells; Administration method: intrapleural infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.; Biological: CEA-targeted CAR-T cells; Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
Experimental: Intraperitoneal infusion of CEA-targeted CAR-T; Infusion of CEA-targeted CAR-T cells by dose of 1-15x10^5 cells/kg	Biological: CEA-targeted CAR-T cells; Administration method: intravenous infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.; Biological: CEA-targeted CAR-T cells; Administration method: intrapleural infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.; Biological: CEA-targeted CAR-T cells; Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]	Incidence of adverse events during the study, evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) criteria	1 month
Obtained the recommended dose and infusion regimen of CAR-T cells for the treatment of patients with CEA-positive advanced malignancies[Safety and Tolerability]	Dose-limiting toxicity after CEA CAR-T cell infusion	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】	Cmax: maximum observed level of circulating CAR-T cells in peripheral blood after infusion	From infusion through Month 3
Assessing disease control rates of CAR-T cell preparations in CEA-positive advanced malignancies [Effectiveness]	Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.	From infusion through Month 3
To evaluate the efficacy of CAR-T cell preparations in CEA-positive advanced malignancies【Effectiveness】	Changes in serum tumor marker levels: CEA, CA19-9, CA-125, etc.	From infusion through Month 3
To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】	To determine the time to maximum observed level of circulating CAR-T cells (Tmax)	From infusion through Month 3
To characterize the in-vivo cellular kinetics of CAR-T cells【pharmacokinetics】	To estimate AUC0-28d and AUC0-90d for circulating CAR-T cells	From infusion through Month 3

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：The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.	2 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	2 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(Assessed based on RECIST criteria)	2 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 (Assessed by investigators based on IRECIST criteria)	2 years

Collaborators and Investigators

• Sponsor: Chongqing Precision Biotech Co., Ltd
• Investigators: Principal Investigator: Donglai Lv, MD, The 901 Hospital of Joint Logistics Support Force of People Liberation Army

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: September 11, 2025
• First Submitted That Met QC Criteria: September 16, 2025
• First Posted (Estimated): September 18, 2025

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 28, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Esophageal Diseases; Stomach Neoplasms; Rectal Neoplasms; Lung Neoplasms; Colonic Neoplasms; Esophageal Neoplasms; Pancreatic Neoplasms
• Other Study ID Numbers: PBC094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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