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

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, 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 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.