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 chemotherapywhere, > 6 months have elapsed between completion of therapy and documented date ofdiagnosis 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 regulationsregarding 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 cardiacconditions.

• Participants with a prior history of hypertensive crisis or hypertensiveencephalopathy or bleeding risks.

• Deep venous thrombosis, pulmonary embolism, arterial thrombosis, transient ischemicattack 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.