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

In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors, anti-LAG3). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be in between approximately 6 and 12 weeks.

Inclusion criteria: * Signed written informed consent * Patients at least 18 years of age * Non-metastatic adenocarcinoma of the colon (and rectosigmoid considered as nonrectal and 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. If biopsies 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 or PD-L1 * For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors at registration and no active peptic ulcer, gastrointestinal bleeding, unstable ischemic heart 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 to any monoclonal antibody, allergy or severe hypersensitivity to NSAIDs or COX2-I (MSS tumors) * No intercurrent illnesses, including but not limited to infections, unstable angina pectoris * No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection * No autoimmune disease * No conditions requiring systemic treatment with either corticosteroids (10 mg daily prednisone or more and equivalents) or other immunosuppressive medications within 14 days of study drug administration * No live vaccines in the 4 weeks prior to inclusion