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

Overall Who May Qualify: - Histopathologically confirmed colorectal adenocarcinoma. - Provision of FFPE tumor sample collected as per SoC. - Presence of measurable disease by RECIST 1.1 criteria. - You should be able to carry out daily activities with 0 level of ability (ECOG 0) or 1. - Life expectancy ≥ 12 weeks at the time of screening. Substudy Who May Qualify: - No radiological evidence of liver metastasis. - No previous cancer treatment that works throughout the body (like chemotherapy) for mCRC, except for neoadjuvant/adjuvant chemotherapy where, \> 6 months have elapsed between completion of therapy and documented date of 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 Who Should NOT Join This Trial: - cancer that has spread to the brain 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 Who Should NOT Join This Trial: - 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. Always talk to your doctor about whether this trial is right for you.