Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and PCSK9 Inhibitor for pMMR/MSS Locally Advanced Mid-low Rectal Cancer

Inclusion Criteria:

1. Sign a written informed consent form and voluntarily join this study;
2. Age 18-75 years old, male or female;
3. Pathologically confirmed adenocarcinoma of the rectum;
4. Clinically staged as II~III stage by MRI (according to the 8th edition of AJCC);
5. Tumor lower edge distance from the anal margin ≤10cm;
6. Able to undergo surgical resection;
7. Able to swallow pills normally;
8. ECOG PS 0-1;
9. No prior anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy,surgery, etc.;
10. Planning to undergo surgical treatment after completing neoadjuvant therapy;
11. No contraindications for surgery;
12. Normal major organ function, including:
13. Blood routine examination (no blood or blood products transfusion within 14 daysbefore the first treatment, no use of G-CSF or other hematopoietic stimulatingfactors for correction):

• Neutrophil count ≥1.5×109/L
• Platelet count ≥100×109/L
• Hemoglobin ≥90 g/L

2. Blood biochemistry:

• Total bilirubin ≤1.5×ULN
• ALT ≤ 2.5×ULN, AST ≤ 2.5×ULN,
• Serum creatinine ≤1.5×ULN, or creatinine clearance rate ≥50 mL/min (Cocheroft-Gault formula)

3. Coagulation function:

• International normalized ratio (INR) ≤ 1.5×ULN
• Activated partial thromboplastin time (APTT) ≤ 1.5×ULN
• Female subjects of childbearing potential should have a negative serumpregnancy test within 72 hours before the start of study drugadministration, and effective contraception should be used during the trialperiod and for at least 3 months after the last dose (such as intrauterinedevices, contraceptive pills, or condoms); for male subjects with femalepartners of childbearing potential, effective contraception should be usedduring the trial period and for 3 months after the last dose.

Exclusion Criteria:

1. History of allergy to monoclonal antibodies, PD-1 monoclonal antibodies, capecitabine,or oxaliplatin;
2. History of receiving or currently receiving any of the following treatments:
3. Any surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.,for tumors;
4. Use of immunosuppressive drugs or systemic steroid therapy to achieveimmunosuppression (dose >10mg/day prednisone or equivalent) within 2 weeks beforethe first use of the study drug; inhalation or local use of steroids and adrenalcortical hormone replacement therapy with a dose >10mg/day prednisone orequivalent is allowed in the absence of active autoimmune diseases;
5. Receipt of attenuated live vaccines within 4 weeks before the first use of thestudy drug;
6. Underwent major surgery or had severe trauma within 4 weeks before the first useof the study drug;
7. Active autoimmune diseases or history of autoimmune diseases, including but notlimited to: interstitial pneumonia, enteritis, hepatitis, pituitary inflammation,vasculitis, nephritis, hyperthyroidism, hypothyroidism (considered for inclusion afterhormone replacement therapy); psoriasis or childhood asthma/allergies that havecompletely resolved and do not require any intervention in adulthood may be consideredfor inclusion, but patients requiring bronchodilators for medical intervention are noteligible for inclusion;
8. History of immunodeficiency, including HIV positive, or acquired or congenitalimmunodeficiency diseases, or history of organ transplantation or allogeneic bonemarrow transplantation;
9. Presence of poorly controlled clinical symptoms or diseases of the heart, includingbut not limited to: (1) NYHA class II or above heart failure, (2) unstable anginapectoris, (3) myocardial infarction within the past year, (4) clinically significantsupraventricular or ventricular arrhythmias that have not been clinically intervenedor poorly controlled after clinical intervention;
10. Severe infection (CTCAE > grade 2) within 4 weeks before the first use of the studydrug, such as severe pneumonia requiring hospitalization, septicemia, complications ofinfection, etc.; baseline chest imaging suggests active pulmonary inflammation,presence of symptoms and signs of infection within 14 days before the first use of thestudy drug or requiring oral or intravenous antibiotic therapy, except forprophylactic use of antibiotics;
11. Active pulmonary tuberculosis infection found through medical history or CTexamination, or a history of active pulmonary tuberculosis infection within the pastyear before enrollment, or a history of active pulmonary tuberculosis infection morethan 1 year ago but without proper treatment;
12. Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (HCV antibodypositive, and HCV RNA higher than the lower limit of detection of the assay);
13. Diagnosed with other malignant tumors within 5 years before the first use of the studydrug, unless they have a low risk of metastasis or death (5-year survival rate > 90%),such as adequately treated basal cell carcinoma or squamous cell skin cancer orcarcinoma in situ of the cervix, may be considered for inclusion;
14. Pregnant or lactating women;
15. Judged by the investigator to have other factors that may lead to prematuretermination of the study, such as having other serious diseases (including mentalillnesses) requiring concomitant treatment, alcoholism, drug abuse, family or socialfactors, factors that may affect the safety or compliance of the subject.