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 cT3-4NanyM0or 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 inthe 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 thathave been cured;

3. Current presence of gastric intestine obstruction, bleeding or perforation whichneed 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, currentlong-term use of systemic corticosteroids or other immunosuppressants;

11. Subjects with known active tuberculosis (TB); suspected active TB should be excludedby clinical examination, known active syphilis infection;

12. Received a live vaccine within 30 days prior to the study, or plan to receive a livevaccine during the study;

13. Local or systemic disease caused by non-malignancy, or disease or symptom secondaryto tumor, that can lead to higher medical risk and/or uncertainty in survival;