Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced Malignant Solid Tumors

NCT05415475 | Unknown Phase 1

• 1 other identifier: PBC034
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is an open-label, single-arm clinical study. The main purpose is to verify the safety and efficacy of CAR-T cell preparations in the treatment of CEA-positive advanced malignant tumors, and to obtain the recommended dose and infusion scheme of CAR-T cell preparations for the treatment of patients with CEA-positive advanced malignant tumors.

Conditions

Colorectal Cancer; Esophageal Cancer; Stomach Cancer; Pancreatic Cancer; Metastatic Tumor; Recurrent 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 (2)

Intravenous of CEA-targeted CAR-T

EXPERIMENTAL

Infusion of CEA-targeted CAR-T cells by dose of 1-10x107 copy/kg

Biological: CEA CAR-T cells

intraperitoneal injection of CEA-targeted CAR-T

EXPERIMENTAL

Infusion of CEA-targeted CAR-T cells by dose of 1-10x107 copy/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 injection of 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, esophageal cancer, gastric cancer, and pancreatic 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%); 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:

• Previous CAR-T therapy or other gene-modified cell therapy；
• 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;

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

Shandong Second Provincial General Hospital

Jinan, Shandong, 250000, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Neoplasm Metastasis; Recurrence

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; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Jingwang Bi, M.D

  Shandong Second Provincial General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jingwang Bi, M.D

CONTACT

13066029387; jingwangbi@live.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 13, 2022
• Study Start: September 10, 2021
• Primary Completion: September 15, 2024
• Study Completion: September 15, 2025
• Last Updated: January 5, 2024

Record last verified: 2023-11

Locations

CN (1)