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.