PD-1–edited tumor-infiltrating T cells for advanced colorectal cancer

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

This test uses a patient's own tumor-infiltrating T cells, edited to remove PD‑1, to see if the treatment is safe and may help adults with advanced colorectal cancer who no longer have standard treatment options.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai, None Selected)
• Trial ID: NCT07035002 on ClinicalTrials.gov

What this trial studies

Tumor tissue is obtained by surgery or biopsy and tumor-infiltrating lymphocytes (TILs) are isolated and expanded under GMP conditions. The TILs are gene-edited to knock out PD‑1, further expanded to defined dose levels, and then infused back into the patient in a dose-escalation Phase 1 design. The trial's primary focus is safety and tolerability, recording adverse events and dose-limiting toxicities, with secondary collection of preliminary anti-tumor activity by RECIST 1.1 and survival outcomes. All manufacturing and treatments are performed at a single site with close clinical monitoring.

Who should consider this trial

Good fit: Adults aged 18–70 with histologically confirmed advanced colorectal cancer who are not eligible for standard therapies, have at least one measurable lesion, ECOG 0–1, adequate organ and marrow function, and are willing to provide tumor tissue by surgery or biopsy.

Not a fit: Patients with poor performance status, life expectancy under six months, uncontrolled infections, recent conflicting anti-cancer treatments, or tumors unlikely to present sufficient neoantigens may not benefit from this approach.

Why it matters

Potential benefit: If successful, PD‑1 knockout TILs could restore tumor-specific T cell activity and produce tumor shrinkage or longer-lasting responses in some patients with refractory colorectal cancer.

How similar studies have performed: TIL therapy has achieved notable responses in melanoma, but PD‑1 gene-edited TILs remain an early-stage experimental approach with limited clinical evidence in colorectal cancer so far.

Eligibility criteria

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;

Where this trial is running

Shanghai, None Selected

• Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, None Selected, China (Recruiting)

Conditions Colorectal Cancer; Tumor Infiltrating Lymphocytes; PD-1