Neoantigen-loaded DC Vaccine and Conventional Second-line Therapy for CRC Progressed After First-line Treatment

Prior treatment

• Subjects expected to require any form of antitumor treatment during the study, including maintenance therapy with other drugs, chemotherapy, and/or surgical resection.
• Subjects who have required systemic treatment with corticosteroids (\>10 mg/day of prednisone or equivalent) or other immunosuppressants within 14 days before the first dose. Inhalational or topical corticosteroids are allowed in the absence of active autoimmune diseases;
• Subjects who have been treated with anticancer immunotherapies or other immunostimulatory anticancer drugs (interferons, interleukins, thymosin, immune cell therapy, etc.) within 3 months before the first dose;
• Subjects participating in other clinical trials or whose first dose is less than 4 weeks (or 5 half-lives of the study drug) after the end of the previous clinical trial (last dose);
• Subjects with severe cardiovascular diseases, such as those meeting NYHA Class II or higher criteria, myocardial infarction, or cerebrovascular accidents (cerebral ischemia, symptomatic cerebral embolism, etc.) occurring within 3 months before the first dose, or unstable arrhythmias or unstable angina within 1 month before starting study treatment;
• Subjects with hypertension that cannot be well controlled by antihypertensive medication (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg) (Note: a stable antihypertensive regimen should be in place within 1 week before the first dose);
• Subjects who have had significant clinically relevant bleeding symptoms or a clear bleeding tendency within 3 months before the first dose, as well as tumors that have invaded major blood vessels or, in the investigator's judgment, are highly likely to invade major blood vessels and cause major bleeding during treatment. Subjects with obvious hemoptysis, coughing up 2.5 mL or more of blood in the month before the first dose;
• Subjects who have experienced arterial/venous thrombotic events, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral embolism), deep vein thrombosis, and pulmonary embolism, within 3 months before screening;
• Subjects who have had a serious infection within 4 weeks before the first dose, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.; Subjects with any active infection;
• Subjects preparing for or who have previously undergone tissue/organ transplantation;
• Subjects with a history of chronic alcohol or drug abuse within 6 months before enrollment;

Other illness

• Disease-specific exclusion criteria:
• Subjects with uncontrolled myocardial ischemia or myocardial infarction, poorly controlled arrhythmias are excluded;
• Subjects with active tuberculosis;
• Subjects with uncontrolled epilepsy, central nervous system disorders, or neurological diseases resulting in cognitive impairment;
• Subjects with a history of splenectomy.
  • Other exclusion criteria:
• Subjects with a severe history of allergies or atopic constitution;

Other

• Patients with uncontrollable brain metastases;
• Pregnant or breastfeeding women;
• Subjects deemed unsuitable for the study by the investigator.

• Patients with histologically or cytologically confirmed CRC;
• At least one measurable lesion;
• Aged 18-70, regardless of gender;
• Disease progression after standard first-line therapy, and more than 2 weeks since the end of the last antitumor treatment;
• Expected survival of ≥3 months;
• ECOG performance status of 0-1;
• Female patients of childbearing age must have a negative pregnancy test and be able to take effective contraceptive measures with no plans for pregnancy within six months of the study;
• Able to undergo all screening period laboratory tests as required by the protocol;
• Normal major organ function, such as heart, liver, and kidney;
• Hematologic parameters: neutrophil count ≥1.5×10\^9/L, hemoglobin ≥10g/dL, platelet count ≥100×10\^9/L, total bilirubin ≤1.5 times the upper limit of normal, AST and ALT ≤2.5 times the upper limit of normal, creatinine and blood urea nitrogen ≤1.5 times the upper limit of normal, activated partial thromboplastin time ≤1.5×ULN, and International Normalized Ratio or prothrombin time ≤1.5×ULN;
• No active hepatitis, AIDS, syphilis, or other infectious diseases;
• Rheumatoid panel: C-reactive protein (CRP) ≤10.0mg/L; Anti-streptolysin O (ASO) \<500U; Erythrocyte sedimentation rate ≤15mm/h (men) or 20mm/h (women);
• Thyroid function tests: 0.27mIU/L ≤ Thyroid-stimulating hormone (TSH) ≤ 4.2mIU/L; 3.1pmol/L ≤ Free triiodothyronine (FT3) ≤ 6.8pmol/L; 12pmol/L ≤ Serum free thyroxine (FT4) ≤ 22pmol/L; 1.3nmol/L ≤ Serum total triiodothyronine (TT3) ≤ 3.1nmol/L; 66nmol/L ≤ Serum total thyroxine (TT4) ≤ 181nmol/L;
• Adrenocorticotropic hormone (ACTH): 1.1-17.6pmol/L;
• Ability to understand and voluntarily sign a written informed consent form.