Overview

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).

Eligibility

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.