IX001 TCR-T In the Treatment of Advanced Pancreatic Cancer and Colorectal Cancer Induced by KRAS Mutations

Brief summary public domain (ClinicalTrials.gov)

This is a single-arm, single-center, open-label clinical study aimed at evaluating the safety and efficacy of IX001 TCR-T (T cell receptor-engineered T-Cell) injection in patients with advanced pancreatic cancer and colorectal cancer induced by KRAS (Kirsten Rat Sarcoma Viral Oncogene) mutations. A total of 6-18 evaluable patients are planned to be enrolled. The study will include 4 dose groups, using a '3+3' dose escalation design.

Detailed description public domain (ClinicalTrials.gov)

Patients who sign the informed consent form will undergo screening based on inclusion/exclusion criteria. Eligible patients will be enrolled sequentially into dose group 1, dose group -1 or dose group 2, and dose group 3. The procedure of this study is as follows: (I) The collected peripheral blood mononuclear cells (PBMCs) will be transported to the production workshop for the preparation of IX001. After confirming that IX001 is proved qualified, the investigator will decide whether to start pre-conditioning 5 days before IX001 infusion. (II) TCR-T cells will be administered via intravenous infusion, and the cell infusion dose will be determined according to the requirements of dose escalation. (III) Following TCR-T cell infusion, recombinant human interleukin-2 (IL-2) will be continuously injected to assist TCR-T cell growth. (IV) After TCR-T cell infusion and IL-2 injection are completed, safety and efficacy follow-up visits will be conducted with the subjects until week 96 or until the subject prematurely withdraws from the study.

Intervention public domain (ClinicalTrials.gov)

Biological: IX001 TCR-T cells. IX001 TCR-T cell injection will be administered intravenously after lymphodepletion.

Arm public domain (ClinicalTrials.gov)

IX001 TCR-T cells (experimental): IX001 TCR-T cells targeted for KRAS mutation

Primary outcome public domain (ClinicalTrials.gov)

Dose-limiting Toxicity (DLT). Proportion of patients with DLT Time frame: 4 weeks.

Primary outcome public domain (ClinicalTrials.gov)

Adverse Events (AEs). Incidence and severity of adverse events Time frame: 96 weeks.

Primary outcome public domain (ClinicalTrials.gov)

Serious Adverse Events (SAEs). Incidence and severity of serious adverse events Time frame: 96 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Objective Response Rate (ORR). Time frame: 12 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate (DCR). Time frame: 12 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Changes in Serum Tumor Markers compared to Baseline. Time frame: 12 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of response (DOR). Time frame: 96 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Time to response (TTR). Time frame: 96 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Progression-free survival (PFS). Time frame: 96 weeks.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Voluntary signing of an informed consent form (ICF); 2. Males or females, aged 18-70 years (inclusive); 3. Pathologically diagnosed with advanced pancreatic cancer or colorectal cancer, having failed or intolerant to at least two lines of standard of care, including metastatic tumors (having received conventional chemotherapy), recurrent tumors (having undergone surgery and adjuvant chemotherapy in the past), or locally advanced tumors with disease progression after neoadjuvant treatment; 4. At least one measurable lesion (according to RECIST1.1\[The Response Evaluation Criteria In Solid Tumors\] criteria); 5. Patients with tumor tissue or peripheral blood testing positive for KRAS-G12V or G12D mutations and expression of matching HLA-A\*11, C\*01:02, or C\*08:02 subtypes; 6. ECOG (Eastern Cooperative Oncology Group)≤2; 7. Life expectancy ≥3 months; 8. Absolute neutrophil count ≥1×10E9/L; 9. Platelet count ≥50×10E9/L, hemoglobin\>90g/dL; 10. Absolute lymphocyte count ≥0.5×10E9/L; 11. Adequate functional reserve of organs: 1. Aspartate aminotransferase ≤2.5×ULN (upper limit of normal); 2. Aspartate transaminase ≤2.5×ULN; 3. Creatinine clearance ≥60mL/min; 4. Total serum bilirubin ≤1.5×UNL; 5. The subject has left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant pericardial effusion diagnosed by echocardiography; 6. No clinically significant electrocardiographic abnormality; 7. Basic oxygen saturation is \>92% under the indoor natural air environment. 12. Women of childbearing age must be negative for blood HCG (Human Chorionic Gonadotropin) pregnancy test (by immunofluorescence method) at screening and baseline periods, and agree to use effective contraception for at least 1 year after infusion; and male subjects whose partners are women of childbearing age must agree to use effective barrier contraception methods and avoid sperm donation for at least 1 year after infusion. Contraception must include one highly effective and one additional effective (barrier) method, initiated from screening until at least 1 year after IX001 infusion or until two consecutive flow cytometry tests show the absence of TCR-T cells (whichever occurs later). Exclusion Criteria: 1. Other malignancies (except non-melanoma skin cancer with the disease-free survival of more than 5 years and cervical carcinoma in situ, bladder cancer, or breast cancer); 2. A history of mental disorders, which may affect compliance with this protocol or …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 0 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

Study was stopped Sponsor discretion. No patients were dosed.