A Phase ll Study of Neoadjuvant Short-course Radiotherapy Followed by Ivonescimab and Chemotherapy in pMMR/MSS Locally Advanced Rectal Cancer

Inclusion Criteria:

1. Age between 18 and 75 years;
2. ECOG perfommance status of 0 or 1;
3. Life expectancy: more than 2 years;
4. Histologically proven rectal adenocarcinoma;
5. Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing;
6. According to the 8th Edition of the AJCC Staging Manual, clinical stage cT3-4NanyM0 or cTxN+M0 of II-III rectal cancer was determined by Magnetic resonance imaging (MRI)±transrectal ultrasonography/ ultrasound endoscopy. Lower edge of the tumor was ≤ 12 cm from the anal verge;
7. Eligible for R0 surgery;
8. No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc;
9. Adequate organ function;
10. Males or females with reproductive ability who are willing to use contraception in the trial;

Exclusion Criteria:

1. Any distant metastasis or inoperable disease, regardless clinical stage;
2. Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured;
3. Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery;
4. Multiple primary rectal cancers;
5. Previous pelvic or abdominal radiotherapy;
6. Difficulty swallowing;
7. Current presence of uncontrolled combined disease;
8. Active clinical infections;
9. History of severe bleeding tendency or coagulation dysfunction;
10. Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants;
11. Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection;
12. Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study;
13. Local or systemic disease caused by non-malignancy, or disease or symptom secondary to tumor, that can lead to higher medical risk and/or uncertainty in survival;