Radiotherapy Combined With Capeox Chemotherapy, Sintilimab and Suvemcitug in Locally Advanced pMMR Rectal Cancer:a Prospective Clinical Trial

Other illness

• 1\) Failure to sign an informed consent form;
  • 2\) Immunohistochemistry of tumor biopsy specimens indicating dMMR or microsatellite instability testing indicating MSI-H;
  • 3\) Preoperative evidence of distant metastasis;
  • 4\) History of severe bleeding tendency or coagulation disorders; patients who have previously or currently require long-term anticoagulant therapy (e.g., patients with atrial fibrillation who have a CHADS2 score of ≥2).
  • 5\) History of myocarditis, cardiomyopathy, or malignant arrhythmias. History of unstable angina, congestive heart failure, or vascular disease (e.g., an aortic aneurysm requiring surgical repair or peripheral venous thrombosis) requiring hospitalization within 12 months prior to study treatment, or other cardiac conditions that may affect the safety evaluation of the study drug (e.g., poorly controlled arrhythmias, myocardial infarction, or ischemia) ;
  • 6\) History of esophageal or fundic varices, severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to study treatment;
  • 7\) History of any arterial thromboembolic event, venous thromboembolism of Grade 3 or higher according to NCI CTCAE Version 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to study treatment;
  • 8)An acute exacerbation of chronic obstructive pulmonary disease (COPD) within 1 month prior to study treatment; current hypertension with a systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg despite treatment with oral antihypertensive medications; severe hypertension that is poorly controlled with medication;
  • 9\) History of HIV infection or active chronic hepatitis B or C, or other active, clinically significant infections;
  • 10\) Subjects with active pulmonary tuberculosis (TB) who are currently receiving antituberculosis therapy or who have received such therapy within 1 year prior to screening;
  • 11\) Cachexia, organ dysfunction;
  • 12\) History of pelvic or abdominal radiation therapy;
  • 13\) Multiple primary colorectal cancers;
  • 14\) Patients with seizures requiring treatment (e.g., with steroids or antiepileptic therapy);
  • 15\) History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ or basal cell carcinoma of the skin;
  • 16\) Substance abuse, or medical, psychological, or social conditions that may interfere with the patient's participation in the study or affect the evaluation of study results;
  • 17\) Known or suspected allergy to the study drug or to any medication administered in connection with this trial;
  • 18\) Any unstable condition or situation that may jeopardize the patient's safety or compliance;Pregnant or breastfeeding women of childbearing potential who are not using adequate contraception.

• 1\) Aged 18-75 years;
  • 2\) ECOG 0-1;
  • 3\) Histologically confirmed rectal adenocarcinoma;
  • 4\) Preoperative staging: cT3-4N0M0 or cT1-4N+M0;
  • 5\) Distance from the tumour's inferior margin to the anus ≤ 12 cm;
  • 6\) Tumour biopsy immunohistochemistry indicates pMMR, i.e. positive expression of all MSH1/MSH2/MSH6/PMS2, and molecular testing indicates MSS (microsatellite-stable).
  • 7\) Haematological parameters: WBC \> 4,000/mm³; PLT \> 100,000/mm³; Hb should, in principle, be \> 10 g/dL; chronic anaemia (haemoglobin \< 10.0 g/dL) is not an exclusion criterion and may be assessed by a multidisciplinary team;
  • 8\) Liver function: Serum total bilirubin ≤ 1.5 × ULN (for subjects with Gilbert's syndrome, total bilirubin ≤ 3 × ULN is allowed)；aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN；
  • 9\) Renal function: serum creatinine ≤ 1.5 × ULN, or creatinine clearance \> 50 mL/min;
  • 10\) Other: not pregnant or breastfeeding; no other malignant diseases within the past 5 years or concurrently (excluding basal cell carcinoma of the skin or cervical carcinoma in situ); no mental illness preventing the provision of informed consent; no concomitant serious diseases that would shorten survival;
  • 11\) No previous surgery, chemotherapy or radiotherapy for rectal cancer;
  • 12\) No previous immunotherapy;
  • 13\) Previous endocrine therapy: no restrictions.