A Study of Novel Study Interventions and Combinations in Participants With Colorectal Cancer

The main purpose of this study is to evaluate the safety and efficacy of novel study interventions and combinations in participants with Colorectal Cancer (CRC).

Overall Inclusion Criteria: * Histopathologically confirmed colorectal adenocarcinoma. * Provision of FFPE tumor sample collected as per SoC. * Presence of measurable disease by RECIST 1.1 criteria. * ECOG performance status of 0 or 1. * Life expectancy ≥ 12 weeks at the time of screening. Substudy Inclusion Criteria: * No radiological evidence of liver metastasis. * No prior systemic therapy for mCRC, prior neoadjuvant/adjuvant chemotherapy is permitted only when given for resected (M0) disease and only after at least 6 months have elapsed since completion of that therapy and diagnosis of recurrent or metastatic disease. * Known pMMR/MSS status (only pMMR/MSS mCRC allowed). * Adequate organ and bone marrow function * Body weight \> 35 kg at screening and at randomization. * Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Overall Exclusion Criteria: * Central nervous system metastases or spinal cord compression * Known history of severe allergy to any monoclonal antibody or study intervention. * Any unresolved toxicity CTCAE Grade ≥ 2 from a previous anticancer therapy. * History of another primary malignancy. Substudy Exclusion Criteria: * Potentially resectable disease with multidisciplinary plan for radical surgery. * Active or prior documented autoimmune or inflammatory disorders or cardiac conditions. * Participants with a prior history of hypertensive crisis or hypertensive encephalopathy or bleeding risks. * Deep venous thrombosis, pulmonary embolism, arterial thrombosis, transient ischemic attack or cerebrovascular accident. * History of abdominal or tracheoesophageal fistula, GI perforation and/or fistulae, or intraabdominal abscess within 6 months prior to randomization. * Prior exposure to immune mediated therapy. * History of active primary immunodeficiency.