Iparomlimab/Tuvonralimab Integrating With Total Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Cancer (IT-TNT)

Inclusion Criteria: 1. Age 18-75 years old, male and female 2. Histologically confirmed pMMR/MSS rectal adenocarcinoma, defined by MRI as clinical stage II (T3-4, N-) or stage III (any T, N+) 3. Tumor within 12 cm of the anal verge with at least one of the following high-risk factors: cT4, cN2, extramural vascular invasion \[EMVI+\], mesorectal fascia involved \[MRF+\], lateral lymph node \[LN+\], tumor deposit, or low rectal cancer (≤5 cm from the anal verge) 4. Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1. 5. No evidence of distant metastases based on chest and abdominal CT or whole body PET-CT examinations 6. No other rectal cancer (e.g., sarcoma, lymphoma, carcinoid, squamous cell carcinoma, neuroendocrine carcinoma, etc.) or synchronous colon cancer 7. Presence of measurable lesions that meet RECIST v1.1 criteria for evaluation. Exclusion Criteria: 1. dMMR or MSI-H patients 2. Myelosuppression without obvious causes 3. Locally advanced rectal cancer without high-risk factors 4. Prior or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) 5. Severe allergic reaction to other monoclonal antibodies 6. Uncontrolled cardiac clinical symptoms or disease 7. Active autoimmune disease or immunodefciencies, known history of organ transplantation or systematic use of immunosuppressive agents 8. Abnormal coagulation (INR\>1.5 or PT\>16s), bleeding tendency or on thrombolytic or anticoagulant therapy 9. Known history and current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonitis, or severely impaired lung function 10. Known history of prior antitumor therapy, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T-cell related therapy, etc. 11. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1-2 antibody-positive), active syphilis infection, active tuberculosis infection, or active hepatitis B virus or hepatitis C virus infection at screening