Study on the Safety and Tolerability of PD-1 Knockout Tumor-infiltrating T Cells (TILs) in the Treatment of Advanced Colorectal Cancer

Plain-language summary

In this Phase 1 study, tumor-infiltrating lymphocytes (TILs) taken from the tumor tissue of patients with advanced colorectal cancer are expanded in the laboratory, gene-edited so that PD-1 is knocked out, and infused back into the patient after quality control. The aim is to examine the safety and tolerability of several cell dose levels given per kilogram of body weight. The study enrolls patients aged 18 to 70 who are no longer eligible for standard treatment and who volunteer for surgery or biopsy to provide tumor tissue.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Recruiting

Sponsor

Ruijin Hospital

Intervention

transfusion of 5×10^8 PD-1 knockout TILs per kg body weight, transfusion of 1×10^9 PD-1 edited TILs per kg body weight, transfusion of 2×10^9 PD-1 edited TILs per kg body weight, transfusion of maximum dose without side effects among group A, B and C

Start date

12/31/2024

Estimated completion

12/1/2026

Countries

China

Related genes

Locations

• Shanghai, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

* Patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage.
* Patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation.
* Aged ≥18 and ≤70 years old.
* At least one tumor lesion that could be evaluated according to RECIST, version 1.1.
* ECOG score was 0 or 1.
* Adequate bone marrow and organ function.
* The expected survival time of the enrolled patients was no less than 6 months.

Exclusion Criteria:

* Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, traditional Chinese medicine with anti-tumor indications and other anti-tumor treatments within 2 weeks before sampling, except the following:

  1. Nitrosourea or mitomycin C within 6 weeks before surgery;
  2. Oral fluorouracils and small molecule targeted drugs for 1 week before surgery.
* Received other unmarketed investigational drug or treatment within 4 weeks before sampling;
* Had undergone major organ surgery (excluding needle biopsy) within 4 weeks before sampling or had significant lesions Trauma, or the need for elective surgery during the trial;
* Received systemic glucocorticoid (prednisone \>10mg/ day or equivalent dose) or other immunosuppressive therapy within 14 days before sampling; Treatment with topical, ocular, intra-articular, nasal, and inhaled glucocorticoids was excluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrast allergy)
* Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferin, etc., within 14 days before sampling;
* Administration of live attenuated vaccine within 4 weeks before sampling;
* The toxicity of previous antineoplastic therapy has not recovered to CTCAE 5.0 grade ≤1 (except for alopecia and other researchers who judged that there was no safety risk);
* Patients with symptomatic central nervous system or leptomeningeal metastases or other evidence of uncontrolled central nervous system or leptomeningeal metastases as judged by the investigator to be ineligible for enrollment;
* Patients with active infection within 1 week before sampling and currently requiring systemic anti-infective treatment;
* A history of immunodeficiency, including positive HIV antibody test;
* Hepatitis B (HBsAg positive and/or hepatitis C (anti-HCV positive) and/or treponema pallidum antibody positive;
* Patients with current interstitial lung disease;
* Has a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

  1. severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, etc.
  2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose of dose.
  3. New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) \<50%, or structural heart disease at high risk as judged by other investigators;
  4. clinically uncontrolled hypertension.
* Patients with active or previous autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and well-controlled type I diabetes;
* Received immunotherapy with grade ≥ 3 irAE;
* Clinically uncontrollable serous cavity effusion, which was judged by the investigator as not suitable for enrollment;
* Known alcohol or drug dependence;
* Persons with mental disorders or poor compliance;
* Pregnant or lactating women;