Overview

This is a two-arm, open label, randomized phase II clinical study. The aim is to evaluate the safety and efficacy of Cadonilimab (a PD-1/CTLA-4 bispecific antibody) combined with XELOX regimen in pMMR locally advanced rectal cancer during the perioperative period. Eligible patients will receive either Cadonilimab plus XELOX or XELOX alone for 4 cycles before and 4 cycles after surgery. The primary endpoint is the pathological complete response rate.

Eligibility

Inclusion Criteria:

• Histologically or pathologically confirmed rectal adenocarcinoma located within 5 to 15cm from the anus with a stage of T3-4a or N+ according to the CT or endoscope
• Mesorectal fascia uninvolved
• Sign the informed consent form
• 18 years and older
• Mismatch repair proficient determined by immunohistochemistry
• No prior treatment
• Performance status: ECOG 0-1
• Good organ function:

        Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/L; Renal
        function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min;
        Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL,
        AST≤2.5×UNL; Ejection fraction at least 50% (or lower limit of normal) by echocardiogram
        Exclusion Criteria:
          -  Other pathological category, such as squamous cancer
          -  Distant metastasis or peritoneum implantation
          -  Have received chemotherapy or radiotherapy in the past
          -  Known to have allergic reactions to any ingredients or excipients of experimental
             drugs
          -  Unable to swallow or under other circumstance which would drug absorption
          -  Other active malignant tumors, excluding those who have been disease free for more
             than 5 years or in situ cancer considered to have been cured by adequate treatment
          -  Have received colorectal cancer surgery
          -  Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or
             hypertension was not controlled, defined as systolic / diastolic blood pressure > 140
             / 90 mmHg after antihypertensive drug
          -  Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class
             III or IV congestive heart failure in the past 12 months
          -  Known to be infected with human immunodeficiency virus (HIV), have acquired
             immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or
             hepatitis C
          -  Pregnant or nursing
          -  May increase the risk associated with participation in the study or administration of
             the study drug or mental illness that may interfere with the interpretation of
             research results
          -  There are other serious diseases that the researchers believe patients cannot be
             included in the study