Iparomlimab and Tuvonralimab Combined With Chemotherapy and Bevacizumab as Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Inclusion Criteria: * The patient voluntarily consents to participate in this study, demonstrates good compliance, is able to meet the trial requirements for observation and follow-up, and has signed the informed consent form; * Age between 18 and 75 years, inclusive, regardless of gender (at the time of signing the informed consent); * ECOG Performance Status (PS) score of 0 or 1; * Expected survival time ≥12 weeks; * Histologically confirmed diagnosis of mid- or upper-rectal adenocarcinoma, with the tumor located 5-12 cm from the anal verge; * Colonoscopic biopsy specimens assessed by the pathology department at the study center show pMMR by immunohistochemistry or MSS by genetic testing (PCR or NGS method); * Clinical staging of cT3-4N0M0 or cTxN+M0; * No prior anti-tumor therapy (including but not limited to radiotherapy, chemotherapy, targeted therapy, or immunotherapy); * At least one measurable lesion: the lesion must have one clearly measurable diameter (recorded as the longest diameter), with the minimum size defined as follows: * CT scan: ≥10 mm (CT slice thickness should not exceed 5 mm); * Malignant lymph nodes: must be pathologically enlarged and measurable, with a short-axis diameter of ≥15 mm on CT (recommended slice thickness ≤5 mm); * Major organ functions must be adequate, meeting the following criteria: Hematology (without hematopoietic growth factors or blood transfusion within 7 days): 1. Neutrophils ≥1.5 × 10⁹/L 2. Platelets ≥100 × 10⁹/L 3. Hemoglobin ≥90 g/L Biochemistry: e) Total bilirubin ≤1.5 × ULN f) AST and ALT ≤2.5 × ULN g) Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault formula) Coagulation: h) Coagulation function must meet the following conditions: INR ≤1.5 PTT or aPTT ≤1.5 × ULN \- Subjects with reproductive potential must use appropriate contraceptive methods during the study and for 120 days after its completion. Female participants must have a negative serum pregnancy test within 7 days before enrollment and must not be breastfeeding. Exclusion Criteria: * Clinical stage cT4b and low rectal cancer (tumor located less than 5 cm from the anal verge); * Prior rectal cancer surgery before enrollment, excluding stoma procedures; * History of malignancy, except for cured carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, or early-stage thyroid cancer; * Severe hypersensitivity or allergic reactions to humanized antibodies or fusion proteins in the past; * Pregnant or breastfeeding women, or women of childbearing potential who are not using contraception; * Diagnosed immunodeficiency or receiving systemic glucocorticoids or other immunosuppressive therapy within 14 days prior to the first dose of study treatment. Physiological doses of glucocorticoids (≤10 mg/day prednisone or equivalent) are allowed; * Active, known, or suspected autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, etc.) are excluded. However, patients with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, or skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia), or conditions not expected to recur without an external trigger, may be enrolled; * Severe pre-existing cardiac conditions, including: congestive heart failure, uncontrolled high-risk arrhythmias, unstable angina, myocardial infarction, or severe valvular heart disease; * Hypertension that is poorly controlled with antihypertensive medication (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). Patients are eligible if BP is well controlled with treatment. Patients with a history of hypertensive crisis or hypertensive encephalopathy are excluded; * Active hepatitis B (HBV DNA ≥2000 IU/ml or 10⁴ copies/ml) or hepatitis C (positive anti-HCV antibody and HCV-RNA above detection threshold); * Active tuberculosis (TB) infection, as determined by chest X-ray, sputum test, and clinical examination. Patients with a history of active TB infection within the past year are excluded even if treated. Those with TB infection more than a year ago are also excluded unless prior anti-TB treatment was appropriate in both duration and regimen; * Major surgery, incisional biopsy, or significant traumatic injury within 28 days prior to randomization; * Imaging indicates tumor invasion of major blood vessels, or in the investigator's opinion, the tumor is likely to invade major blood vessels during the study and pose a risk of fatal hemorrhage; * Any signs or history of bleeding disorders, regardless of severity; patients who had any bleeding event ≥ Grade 3 (CTCAE) within 4 weeks prior to randomization; patients with unhealed wounds, ulcers, or fractures; * Arterial or venous thrombotic events (e.g., stroke, transient ischemic attack, deep vein thrombosis, or pulmonary embolism) within the past 6 months; * Uncontrolled neurological or psychiatric disorders or mental illness leading to poor compliance or inability to report treatment response; * Any comorbid condition that, in the investigator's judgment, could seriously jeopardize patient safety or interfere with study completion; * Other conditions deemed inappropriate for enrollment by the investigator.