A Study of Encorafenib Plus Cetuximab Taken Together With Pembrolizumab Compared to Pembrolizumab Alone in People With Previously Untreated Metastatic Colorectal Cancer

Inclusion Criteria:

• Locally confirmed microsatellite instability-high/ deficient mismatch repair (MSI-H/dMMR) stage IV colorectal carcinoma

• Locally confirmed BRAF V600E mutation in tumor tissue or blood

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Have not received prior systemic regimens for metastatic disease.

• Measurable disease per RECIST 1.1

• Adequate organ function

Exclusion Criteria:

• Colorectal adenocarcinoma that is RAS mutant or for which RAS mutation status isunknown

• Known active central nervous system metastases and/or carcinomatous meningitis;leptomeningeal disease

• Immunodeficiency or active autoimmune disease requiring systemic treatment in thepast 2 years

• Presence of acute or chronic pancreatitis

• Clinically significant cardiovascular diseases (eg, thromboembolic orcerebrovascular accident events ≤ 12 wks prior)

• Received a live or live-attenuated vaccine within 30 days of planned start of studymedication

• Previous treatment with any selective BRAF inhibitor (eg, encorafenib, dabrafenib,vemurafenib, XL281/BMS-908662) or any epidermal growth factor receptor (EGFR)inhibitor (eg, cetuximab, panitumumab).

• Previous treatment with an immune checkpoint inhibitor (eg, anti-programmed celldeath [PD-1], anti-PD-L1 or anti-PD-L2 agent); or with an agent directed to anotherstimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).