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

Inclusion Criteria:

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

Exclusion Criteria:

1. Rectal tumours (as defined by the presence of the inferior pole of the tumour belowthe peritoneal reflection - that is, <15 cm from the anal margin).
2. Inability to start adjuvant chemotherapy within 12 weeks after surgery
3. Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgicalresection of colon cancer
4. Prior organ transplantation, including allogeneic stem-cell transplantation
5. Significant acute or chronic infections including, among others: known history of testing positive test for human immunodeficiency virus (HIV) or knownacquired immunodeficiency syndrome (AIDS) positive test for HBV (Hepatitis B) surfaceantigen or anti-HCV (Hepatitis C) antibody and confirmatory HCV RNA test
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatoryagent:
7. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease notrequiring immunosuppressive treatment are eligible
8. Subjects requiring hormone replacement with corticosteroids are eligible if thesteroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg/day of prednisone or equivalent
9. Administration of steroids through a route known to result in a minimal systemicexposure (topical, intranasal, intro-ocular, or inhalation) are acceptable ≥3 NCI-CTCAEv4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more featuresof partially controlled asthma)
10. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v4.0; however,alopecia and sensory neuropathy Grade ≤2 is acceptable unless oxaliplatinadministration is planned as part of the adjuvant treatment
11. Pregnancy or lactation
12. Known alcohol or drug abuse
13. Clinically significant (i.e., active) cardiovascular disease: cerebral vascularaccident/stroke (<6 months prior to enrollment), myocardial infarction (<6 monthsprior to enrollment), unstable angina, congestive heart failure (≥ New York HeartAssociation Classification Class II), or serious cardiac arrhythmia requiringmedication
14. 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 informedconsent 17.Other invasive malignancy within 2 years except for non-invasive malignanciessuch as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductalcarcinoma in situ of the breast that has/have been surgically cured.