Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer

Inclusion criteria:

• Signed written informed consent
• Patients at least 18 years of age
• Non-metastatic adenocarcinoma of the colon (and rectosigmoid considered as nonrectaland not undergoing neoadjuvant treatment)
• No signs of distant metastases on CT-scan and physical examination;
• dMMR cohorts 3+6: >cT3 and/or N+

Exclusion criteria:

• No signs of distant metastases
• No signs of obstruction or macroscopic bleeding or suspicion of perforation
• Colonoscopy must be performed after registration to obtain study-specific biopsies. Ifbiopsies are not possible, patients cannot be included in the study
• WHO performance status of 0 or 1
• No previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 orPD-L1
• For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors atregistration and no active peptic ulcer, gastrointestinal bleeding, unstable ischemicheart disease of thrombus etiology or significant established ischemic heart disease,peripheral arterial disease and/or cerebrovascular disease
• No radiotherapy prior to or planned post-surgery radiotherapy
• No history of allergy to study drug components, severe hypersensitivity reaction toany monoclonal antibody, allergy or severe hypersensitivity to NSAIDs or COX2-I (MSStumors)
• No intercurrent illnesses, including but not limited to infections, unstable anginapectoris
• No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virusribonucleic acid (HCV antibody) indicating acute or chronic infection
• No autoimmune disease
• No conditions requiring systemic treatment with either corticosteroids (10 mg dailyprednisone or more and equivalents) or other immunosuppressive medications within 14days of study drug administration
• No live vaccines in the 4 weeks prior to inclusion