PACE: PD-1 Antibody For dMMR/MSI-H Stage III Colorectal Cancer

Prior treatment

• Inability to start adjuvant chemotherapy within 12 weeks after surgery
• Prior organ transplantation, including allogeneic stem-cell transplantation
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg/day of prednisone or equivalent
• Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
• Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v4.0; however, alopecia and sensory neuropathy Grade ≤2 is acceptable unless oxaliplatin administration is planned as part of the adjuvant treatment
• Known alcohol or drug abuse
• Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication

Other illness

• Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgical resection of colon cancer
• Significant acute or chronic infections including, among others:
  • known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) positive test for HBV (Hepatitis B) surface antigen or anti-HCV (Hepatitis C) antibody and confirmatory HCV RNA test
• Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3 NCI-CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
• Known history of colitis, pneumonitis and pulmonary fibrosis (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the 16.Investigator, might impair the subject's tolerance of trial treatment.
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent 17.Other invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.

Other

• Rectal tumours (as defined by the presence of the inferior pole of the tumour below the peritoneal reflection - that is, \<15 cm from the anal margin).
• Pregnancy or lactation

• Male or female subjects aged ≥18 years
• ECOG PS 0/1
• Histologically proven, stage III (i.e., any T, N1 or N2, M0) adenocarcinoma of the colon (as defined by the presence of the inferior pole of the tumour above the peritoneal reflection - that is, at least 10 cm from the anal margin).
• Fully surgically resected tumour with clear resection margins (i.e., \>1 mm)
• Locally confirmed defective mismatch repair (dMMR) tumour (as defined by the lack of staining on either the pre-operative biopsy samples or resection specimens of at least one of the following proteins: MLH1 (mutL homolog 1), MSH2 (mutS homologue 2), MSH6 (mutS homolog 6), PMS2
• Absence of metastases as shown by post-operative CT scan
• Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy