Personalized T-Cell Therapy iNeo-Vac-T01 in Advanced Colorectal Cancer

Evaluation of Feasibility, Safety, and Efficacy of Tumor Neoantigen-Based Personalized T-Cell Therapy iNeo-Vac-T01 in Patients With Advanced Colorectal Cancer

The primary objective of this study is to evaluate the feasibility, safety, and efficacy of personalized T-cell therapy based on tumor neoantigens in patients with advanced colorectal cancer, so as to provide a novel individualized therapeutic strategy for such patients.

Inclusion Criteria

1. Aged ≥ 18 years and ≤ 70 years;

2. Patients with pathologically and radiologically confirmed advanced colorectal cancer, with at least one measurable lesion on imaging;

3. Failure of standard therapy, ineligibility for standard therapy, or refusal to receive standard therapy;

4. Expected survival of at least 6 months;

5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;

6. Sufficient tumor tissue sample available for genomic analysis, or existing whole-genome/whole-exome/transcriptome sequencing data of tumor and normal tissues that meet analytical requirements;

7. Normal function of major organs including heart, liver, and kidney;

8. Normal hematological parameters:

   Neutrophil count ≥ 1.5 × 10⁹/L Hemoglobin ≥ 10 g/dL Platelet count ≥ 100 × 10⁹/L

9. Normal biochemical parameters:

   Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ≤ 3 × ULN allowed in patients with liver metastasis AST and ALT ≤ 2.5 × ULN; ≤ 5 × ULN allowed in patients with liver metastasis Serum creatinine and blood urea nitrogen (BUN) ≤ 1.5 × ULN

10. For women of childbearing potential:

    negative pregnancy test within 7 days before enrollment, no intention to become pregnant in the near term, and willingness to use effective contraception during the study; Pregnant or lactating women are excluded.

11. Male patients willing to use appropriate contraceptive measures;

12. Ability to comply with the study protocol and follow-up procedures.

Exclusion Criteria

1. Unwilling to sign the informed consent form.

2. Concurrent malignancy other than the following:

   cured basal cell carcinoma, thyroid cancer, cervical dysplasia, and disease-free for more than 5 years with low risk of recurrence in the investigator's judgment.

3. No actionable neoantigens identified for personalized immunotherapy after sequencing data analysis.

4. History of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation.

5. Concomitant use of any other anticancer drugs, investigational anticancer therapy, or immunosuppressive agents; long-term use of systemic glucocorticoids.

6. Symptomatic or untreated known brain metastasis or other central nervous system (CNS) metastases.

   Patients with completely resected and/or irradiated CNS metastases that are stable or improved (radiologically stable for at least 4 weeks prior to randomization by CT/MRI, no evidence of cerebral edema, and no requirement for glucocorticoids or anticonvulsants) are eligible.

7. Received other vaccinations within 4 weeks prior to treatment (except COVID-19 vaccine).

8. Clinically confirmed active bacterial or fungal infection; active tuberculosis or history of tuberculosis.

9. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA titer above the normal range; positive hepatitis C virus (HCV) antibody with peripheral blood HCV RNA above the normal range; positive human immunodeficiency virus (HIV) antibody; positive syphilis test.

10. Severe asthma, autoimmune disease, or immunodeficiency requiring immunosuppressive therapy.

    Excluded: vitiligo, type 1 diabetes, autoimmune hypothyroidism controlled by hormones, psoriasis not requiring systemic therapy.

11. Known history of primary immunodeficiency.

12. History of psychiatric disorder.

13. Uncontrolled comorbidities including but not limited to:

    active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia; severe coronary artery disease or cerebrovascular disease; or other conditions deemed ineligible by the investigator.

14. Substance abuse, or clinical, psychological, or social factors that would compromise informed consent or compliance with the study.

15. History of severe allergy to food, drugs, or vaccines, or other potential allergy to immunotherapy in the investigator's judgment.

16. Patients considered ineligible by the investigator or unlikely to complete the study for other reasons.