Colorectal Cancer (CRC)
Conditions
Keywords
Colorectal cancer
Brief summary
This study is a single-arm, single-center investigator-initiated trial (IIT) designed to evaluate the safety and preliminary efficacy of CDH17/GUCY2C CAR-T cell therapy in patients with advanced colorectal cancer, as well as to assess its pharmacodynamic (PD) and pharmacokinetic (PK) profiles.
Interventions
BIOLOGICALCAR-T
Eligible subjects who successfully passed screening will receive CAR-T cell infusion on Day 0 after lymphodepleting preconditioning chemotherapy.
Sponsors
Guangzhou Bio-gene Technology Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily participate in this trial, sign the informed consent form. 2. Advanced colorectal cancer patients who have either failed standard treatment, experienced intolerable toxicity, or are unsuitable or unwilling to undergo standard treatment, and voluntarily agree to receive the current treatment. 3. Be able to provide immunohistochemical (IHC) test results from the past 2 years, indicating positive expression of CDH17/GUCY2C targets in tumor tissues. 4. Have at least one extracranial, measurable/assessable lesion according to RECIST 1.1 criteria. 5. Have an ECOG (Eastern Cooperative Oncology Group) performance status score of 0-1 and an expected survival duration of at least 3 months. 6. Have recovered from the toxicity associated with previous treatments, with a CTCAE toxicity grade of less than 2. 7. Have no significant hematopoietic dysfunction and possess adequate organ function. 8. Be able to meet the research center's requirements for apheresis/peripheral blood collection upon successful screening, or have acceptable stored blood cell separation products available.
Exclusion criteria
1. Patients who have had or currently have other malignant tumors within the past five years. 2. Presence of brain metastasis. 3. History of clinically significant central nervous system disorders, either in the past or at screening. 4. Imaging indicating tumor invasion of major blood vessels or indistinct borders with blood vessels. 5. Individuals who have received cytotoxic drugs or other interventions, assessed by the investigator as potentially impacting lymphocyte expansion, within 14 days or at least five half-lives (whichever is shorter) prior to blood collection for CAR-T preparation. 6. Presence of other viremias. 7. History of severe allergies. 8. Patients with severe cardiac disease. 9. Patients with severe hepatic and renal dysfunction or disorders of consciousness. 10. Patients with active autoimmune or inflammatory diseases. 11. Patients with objective evidence of past or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, severe lung function impairment, etc. 12. Patients who have undergone or are awaiting organ transplantation. 13. Infections requiring intravenous antibiotic therapy for control or are uncontrollable. 14. Individuals who have received live (attenuated) virus vaccines within four weeks prior to screening. 15. Alcoholics or individuals with a history of substance abuse. 16. Pregnant or lactating women. 17. Individuals who have participated in other clinical trials involving drugs within the past 30 days. 18. Patients who, based on the investigator's judgment and/or clinical standards, have contraindications to any study procedures or present other medical conditions that may pose unacceptable risks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Safety | Up to 1 year after CAR-T infusion | Count the Incidence of adverse events |
| Effectiveness evaluation | Up to 1 years after CAR-T infusion | In accordance with the RECIST 1.1 criteria for assessing the efficacy of solid tumors, the objective response rate (ORR), encompassing patients achieving complete response (CR) and partial response (PR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters | Up to 1 year after CDH17/GUCY2C CAR-T infusion | The highest concentration of CAR-T cell expansion in peripheral blood after administration |
| Pharmacodynamic parameters | Up to 1 year after CAR-T infusion | The peak values of CAR-T-related cytokines, which include at least IL-6 and IFN-γ. |
Countries
China
Outcome results
None listed