To Explore the Efficacy of Sintilimab Combined with Bevacizumab in Rectal Cancer

Inclusion Criteria:

• Cohort A:

Rectal cancer patients who have previously received perioperative XELOX regimen treatment.

• Cohort B:

1.Signed written informed consent prior to any trial-related procedures;

2.Non-bedridden cases, regardless of gender, aged 18-75 years;

3.Pathologically confirmed rectal adenocarcinoma, excluding anal squamous cellcarcinoma;

4.No prior antitumor treatment for rectal cancer. For those with Lynch syndrome, noantitumor treatment has been administered for the colorectal cancer related to thisdiagnosis;

5.Based on high-resolution MRI, classified as T1-3bN1-2 or T3aN0 or T3bN0; noinvolvement of the levator ani muscle; negative mesorectal fascia (MRF) status;negative extramural vascular invasion (EMVI); no cancerous nodules;

6.ECOG performance status of 0-1;

7.Expected survival time > 3 months;

8.Adequate organ function, with subjects meeting the following laboratory criteria:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without using granulocytecolony-stimulating factor in the past 14 days.

2. Platelet count ≥ 100 x 10^9/L without transfusion in the past 14 days.

3. Hemoglobin > 9 g/dL without transfusion or use of erythropoietin in the past 14days;

4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN); if total bilirubin > 1.5 ×ULN but direct bilirubin ≤ ULN, enrollment is also allowed;

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (patients with liver metastases are allowed if ALT or AST ≤ 5 × ULN);

6. Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by theCockcroft-Gault formula) ≥ 60 ml/min;

7. Good coagulation function, defined as an international normalized ratio (INR)or prothrombin time (PT) ≤ 1.5 × ULN;

8. Normal thyroid function, defined as thyroid-stimulating hormone (TSH) withinnormal range. If baseline TSH is outside the normal range, subjects can stillbe enrolled if total T3 (or FT3) and FT4 are within normal range;

9. Normal levels of cardiac enzyme profile (subjects may still be enrolled if theinvestigator judges the laboratory abnormality to be of no clinicalsignificance); (optional) 9.For female subjects of childbearing potential, a urine or serum pregnancytest must be performed within 3 days prior to the first dose of theinvestigational drug (Day 1 of Cycle 1) with a negative result. If the urinepregnancy test result cannot be confirmed as negative, a blood pregnancy testis required. Non-childbearing potential females are defined as those who havebeen postmenopausal for at least one year, or have undergone surgicalsterilization or hysterectomy; 10.If there is a risk of conception, all subjects (regardless of gender) mustuse contraception with a failure rate of less than 1% throughout the treatmentperiod and until 120 days after the last dose of the investigational drug (or 180 days after the last dose of chemotherapy).

Exclusion Criteria:

1. Diagnosed with malignant diseases other than rectal cancer within 5years prior to the first administration (excluding cured basal cellcarcinoma of the skin, squamous cell carcinoma of the skin, and/orcompletely excised in situ carcinoma); 2.Currently participating inan interventional clinical study treatment, or received otherinvestigational drugs or used investigational devices within 4 weeksprior to the first administration; 3.Previously received thefollowing therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, ordrugs targeting another stimulus or co-inhibitory T cell receptors (including but not limited to CTLA-4, OX-40, CD137, etc.); 4.Receivedtraditional Chinese medicine or immunomodulatory drugs withanti-tumor indications (including thymosin, interferon, interleukin,except for local use to control pleural effusion) within 2 weeksprior to the first administration. 5.Experienced active autoimmune diseases requiring systemic treatment (e.g.,use of disease-modifying drugs, glucocorticoids, or immunosuppressants) within 2 years prior to the first administration. Alternative therapies (e.g., thyroidhormone, insulin, or physiological glucocorticoids for adrenal or pituitaryinsufficiency) are not considered systemic treatment; 6.Receiving systemic glucocorticoid treatment within 7 days prior to the firstadministration of the study (excluding nasal, inhaled, or other forms of localglucocorticoids) or any other form of immunosuppressive therapy;Note: Physiological doses of glucocorticoids (≤10 mg/day of prednisone orequivalent) are allowed; 7.Presence of clinically uncontrollable abdominal effusion (patients who do notrequire drainage of effusion or who have not shown significant increase ineffusion after stopping drainage for 3 days may be included); 8.Known history of allogeneic organ transplantation (except for cornealtransplantation) or allogeneic hematopoietic stem cell transplantation; 9.Known allergy to the study drugs sintilimab, bevacizumab, or any activeingredients or excipients related to these investigational drugs; 10.Presence of multiple factors affecting oral medication (e.g., inability toswallow, post-gastrointestinal resection, chronic diarrhea, and bowelobstruction); 11.Not fully recovered from any toxicity and/or complications arising from anyintervention prior to the start of treatment (i.e., ≤ grade 1 or return tobaseline, excluding fatigue or hair loss); 12.Known history of human immunodeficiency virus (HIV) infection (i.e.,positive for HIV 1/2 antibodies); 13.Untreated active hepatitis B (defined as HBsAg positive with HBV-DNA copiesexceeding the upper limit of normal for the testing laboratory at the studysite);Note: Hepatitis B subjects meeting the following criteria may also be included:HBV viral load <1000 copies/ml (200 IU/ml) prior to the first administration;subjects should receive anti-HBV treatment throughout the study drug treatmentperiod to prevent viral reactivation.Subjects with anti-HBc (+), HBsAg (-), anti-HBs (-), and HBV viral load (-) donot need to receive prophylactic anti-HBV treatment but require closemonitoring for viral reactivation. 14.Active HCV infection subjects (HCV antibody positive and HCV-RNA level abovethe lower limit of detection); 15.Received live vaccine within 30 days prior tothe first administration (Cycle 1, Day 1); Note: Inactivated virus vaccine forseasonal influenza is allowed within 30 days prior to the first administration;however, intranasal live attenuated influenza vaccine is not permitted. 16.Pregnant or breastfeeding women; 17.Presence of any severe or uncontrolledsystemic diseases, such as:

2. Significant abnormalities in rhythm, conduction, or morphology on resting ECGthat are severe and symptomatic, such as complete left bundle branch block,second-degree or higher heart block, ventricular arrhythmia, or atrialfibrillation;

3. Unstable angina, congestive heart failure, chronic heart failure classified asNYHA class ≥ 2;

4. History of any arterial thrombosis, embolism, or ischemia within 6 months priorto enrollment, such as myocardial infarction, unstable angina, cerebrovascularaccident, or transient ischemic attack;

5. Poorly controlled blood pressure (systolic blood pressure > 140 mmHg, diastolicblood pressure > 90 mmHg);

6. History of non-infectious pneumonia requiring glucocorticoid treatment within 1year prior to the first administration, or current clinically activeinterstitial lung disease;

7. Active pulmonary tuberculosis;

8. Presence of active or uncontrolled infections requiring systemic treatment;Clinically active diverticulitis, abdominal abscess, gastrointestinalobstruction;

9. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronicactive hepatitis;

10. Poorly controlled diabetes (fasting blood glucose (FBG) > 10 mmol/L);Urinalysis indicating urine protein ≥ ++, confirmed by 24-hour urine proteinquantification > 1.0 g;

11. Presence of mental disorders and inability to cooperate with treatment;

12. Any history or evidence of disease that may interfere with study results,hinder subject participation throughout the study, abnormal treatment orlaboratory test values, or other conditions deemed unsuitable for enrollment bythe investigator due to potential risks.