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

Inclusion criteria

• Aged ≥ 18 years and ≤ 70 years;
• Patients with pathologically and radiologically confirmed advanced colorectal cancer, with at least one measurable lesion on imaging;
• Failure of standard therapy, ineligibility for standard therapy, or refusal to receive standard therapy;
• Expected survival of at least 6 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• 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;
• Normal function of major organs including heart, liver, and kidney;
• Normal hematological parameters:

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

• 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

• 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.

• Male patients willing to use appropriate contraceptive measures;
• Ability to comply with the study protocol and follow-up procedures.

Exclusion criteria

• Unwilling to sign the informed consent form.
• 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.

• No actionable neoantigens identified for personalized immunotherapy after sequencing data analysis.
• History of bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation.
• Concomitant use of any other anticancer drugs, investigational anticancer therapy, or immunosuppressive agents; long-term use of systemic glucocorticoids.
• 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.

• Received other vaccinations within 4 weeks prior to treatment (except COVID-19 vaccine).
• Clinically confirmed active bacterial or fungal infection; active tuberculosis or history of tuberculosis.
• 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.
• Severe asthma, autoimmune disease, or immunodeficiency requiring immunosuppressive therapy.

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

• Known history of primary immunodeficiency.
• History of psychiatric disorder.
• 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.

• Substance abuse, or clinical, psychological, or social factors that would compromise informed consent or compliance with the study.
• History of severe allergy to food, drugs, or vaccines, or other potential allergy to immunotherapy in the investigator's judgment.
• Patients considered ineligible by the investigator or unlikely to complete the study for other reasons.