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

Inclusion criteria

• Age between 18 and 75 years;
• ECOG perfommance status of 0 or 1;
• Life expectancy: more than 2 years;
• Histologically proven rectal adenocarcinoma;
• Tumor biopsy immunohistochemistry proven pMMR, positive for four proteins, MLH1, MSH2, MSH6 and PMS2, or MSS determined by gene testing;
• 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;
• Eligible for R0 surgery;
• No prior anti-tumor treatment for rectal cancer,including radiotherapy,chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc;
• Adequate organ function;
• Males or females with reproductive ability who are willing to use contraception in the trial;

Exclusion criteria

• Any distant metastasis or inoperable disease, regardless clinical stage;
• Previous (within 5 years) or concurrent other malignant tumors, excluding those that have been cured;
• Current presence of gastric intestine obstruction, bleeding or perforation which need emergency surgery;
• Multiple primary rectal cancers;
• Previous pelvic or abdominal radiotherapy;
• Difficulty swallowing;
• Current presence of uncontrolled combined disease;
• Active clinical infections;
• History of severe bleeding tendency or coagulation dysfunction;
• Presence or history of immunodeficiency; positive for HIV antibodies, current long-term use of systemic corticosteroids or other immunosuppressants;
• Subjects with known active tuberculosis (TB); suspected active TB should be excluded by clinical examination, known active syphilis infection;
• Received a live vaccine within 30 days prior to the study, or plan to receive a live vaccine during the study;
• 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;