Safety and Efficacy of CEA-targeted CAR-T for CEA-positive Advanced Malignant Solid Tumors

NCT05538195 | Unknown Phase 1

• 1 other identifier: PBC040
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Cancer; Colon Cancer; Rectal Cancer; Esophageal Cancer; Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety of CAR-T cell preparations in the treatment of CEA-positive advanced malignancies [Safety and Tolerability]

  The incidence of adverse events after CEA CAR-T cell infusion was assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0)

  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

  28 days

Secondary Outcomes (5)

• Assessing disease control rates of CAR-T cell preparations in CEA-positive advanced malignancies[Effectiveness]

  3 month

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

  3 months

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

  3 months

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

  3 months

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

  3 months

Other Outcomes (4)

• 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 3-10x10\^6 cells/kg

Biological: CEA-targeted CAR-T cells

intraperitoneal injection of CEA-targeted CAR-T

EXPERIMENTAL

Infusion of CEA-targeted CAR-T cells by dose of 1-10x10\^6 cells/kg

Biological: CEA-targeted CAR-T cells

Interventions

CEA-targeted CAR-T cells BIOLOGICAL

Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.

Intravenous 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 failure (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 positive rate ≥ 10%), the serum CEA of the patient is required to 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\>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;
• 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 patients with liver tumor infiltration, it can be relaxed to ≤5.0×ULN);
• Total bilirubin≤3.0×ULN;
• Oxygen saturation ≥95% 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 a history of unexplained syncope (except those caused by vasovagal 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 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;
• Women who are pregnant or breastfeeding;

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

He'nan Cancer Hospital

Henan, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Esophageal Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Ning Li, MD

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ning Li, MD

CONTACT

13526501903; lining97@126.com

Yijie Ma, MM

CONTACT

15038279901; mayijie1987@126.com

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: September 9, 2022
• First Posted: September 13, 2022
• Study Start: June 7, 2022
• Primary Completion: December 30, 2024
• Study Completion: June 7, 2025
• Last Updated: September 13, 2022

Record last verified: 2022-05

Locations

CN (1)