Summary

The purpose of this study is to evaluate two study medicines (encorafenib plus cetuximab)
taken alone or together with standard chemotherapy for the potential treatment of colorectal
cancer that:

- has spread to other parts of the body (metastatic);

- has a certain type of abnormal gene called "BRAF"; and

- has not received prior treatment.

Participants in this study will receive one of the following study treatments:

- Encorafenib plus cetuximab: These participants will receive encorafenib by mouth at home
every day and cetuximab once every two weeks by intravenous (IV) infusion (an injection
into the vein) at the study clinic.

- Encorafenib plus cetuximab with chemotherapy: These participants will receive
encorafenib and cetuximab in the way described in the bullet above. Additionally, they
will receive standard chemotherapy by IV infusion and oral treatment at home.

- Chemotherapy alone: These participants will receive chemotherapy, the standard treatment
for this condition, by IV infusion at the study clinics and oral treatment at home.

This study is currently enrolling participants who will receive either encorafenib plus
cetuximab with chemotherapy or chemotherapy alone.

The study team will monitor how each participant responds to the study treatment for up to
about 3 years.

Objectives

The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in
combination with chemotherapy, can improve clinical outcomes relative to current standard
of-care chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC. Since
encorafenib has not previously been combined with chemotherapy, the tolerability and PK of EC
in combination with mFOLFOX6 and in combination with FOLFIRI will be evaluated in separate
cohorts in the safety lead-in portion of the trial in order to identify which chemotherapy
combination is to be used in the Phase 3 portion of the study.