Neoadjuvant Treatment With mFOLFOXIRI Plus Cadonilimab (AK104) Versus mFOLFOX6 in Locally Advanced Colorectal Cancer

Inclusion Criteria:

1. Aged 18-70;
2. Colorectal adenocarcinoma with definite histological evidence;
3. ECOG Performance status score is 0-1
4. Colon cancer was evaluated as T3>5mm or T4 by contrast-enhanced CT examination of thechest, abdomen and pelvis, and distant displacement was excluded; Rectal cancer wasgraded as T3-4 and/or N+ by pelvic contrast-enhanced MRI examination, and the lowermargin of the tumor was less than 12cm away from the anal margin. Distant metastasiswas excluded by chest, abdomen and pelvis CT.
5. The primary rectal tumor was assessed as complete resections by a multidisciplinarycollaboration group on colorectal cancer, including at least 2 gastrointestinalsurgeons and 1 radiologist;
6. No previous systemic antitumor therapy for colorectal cancer, including cytotoxicdrugs, immunotherapy, molecular targeted therapy, etc.;
7. Adequate organ function based on the following laboratory test values obtained within 7 days prior to treatment: Hemoglobin ≥90g/L, neutrophil count ≥1.5×109/L, platelet count ≥75×109/L, serum totalbilirubin ≤1.5× upper limit of normal value (UNL), aspartate transferase ≤2×UNL,alanine transferase ≤3×UNL, serum creatinine ≤1.5×UNL;
8. Willing and able to comply with research protocols and visit plans.

Exclusion Criteria:

1. The patient was complicated with obstruction, active bleeding, or perforation andrequired emergency surgery or stent placement;
2. Active, known or suspected autoimmune diseases (except type I diabetes, residualhypothyroidism requiring only hormone replacement due to autoimmune conditions, orautoimmune diseases that are not expected to recur in the absence of externaltriggers);
3. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiencysyndrome (AIDS), untreated active hepatitis (hepatitis B, defined as HBV-DNA ≥ 500IU/ml; Hepatitis C, defined as HCV-RNA above the detection limit of the assay) orco-infection with hepatitis B and C;
4. Known allergy to the treatment drug or allergy or intolerance to its ingredients;
5. Major surgery or severe trauma, such as laparotomy, thoracotomy, laparoscopic organresection, etc. within the previous 4 weeks (the surgical incision should becompletely healed before enrollment);
6. Existing or coexisting other active malignancies (except those that have been treatedwith curative therapy and remain disease-free for more than 5 years or carcinoma insitu that can be cured by adequate treatment);
7. Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody andanti-cytotoxic T-lymphocyte-associated protein 4 (Cytotoxic T-lymphocyte-associatedprotein 4) antibody. Ctla-4) antibodies or other drugs/antibodies that act on T-cellcostimulatory or checkpoint pathways;
8. Had active coronary artery disease, severe/unstable angina pectoris or newly diagnosedangina pectoris or myocardial infarction within 6 months prior to study enrollment;Thrombotic or embolic events, such as cerebrovascular accident (including transientischemic attack), pulmonary embolism, deep vein thrombosis, occurred within theprevious 6 months;
9. The New York Heart Association (NYHA) class II or higher congestive Heart failure (seeAppendix 3);
10. Presence of active inflammatory bowel disease or other colorectal disease leading tochronic diarrhea;
11. The presence of any toxicity (Common Terminology Criteria for Adverse Events, CTCAE) (version 5.0) grade 1 or above (except anemia, alopecia, and skin pigmentation) causedby previous treatment that has not subsided;
12. Previous or current history of pulmonary fibrosis, interstitial pneumonia,pneumoconiosis, drug-related pneumonia, severe impairment of pulmonary function andother lung diseases;
13. Active tuberculosis (TB), receiving anti-TB therapy or receiving anti-TB therapywithin 1 year before the first dose;
14. Persons with known syphilis infection requiring treatment;
15. Had used immunosuppressive drugs within 4 weeks before the first dose, Does notinclude the nasal spray, inhalation, or other ways of topical corticosteroids orphysiological doses of systemic corticosteroids (i.e., no more than 10 mg/dayprednisone or other equivalent dose glucocorticoids), allows for prevention ofallergic reactions, or treatment of diseases such as asthma, chronic obstructivepulmonary disease of breathing difficulties for the temporary use of glucocorticoid;
16. Receive live attenuated vaccine within 4 weeks before the first dose or during thestudy period;
17. Pregnant or lactating women; Women of reproductive age (< 2 years after lastmenstruation) who do not use or refuse to use effective non-hormonal contraception ormen at risk of having children.