BREAKWATER C4221015

Metastatic colorectal cancer

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.

Inclusion

• Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation
• Participants who have received ≤1 (Safety Lead-In) or no (Phase 3) prior systemic regimens for metastatic disease. 
• Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis < 6 month from end of adj/neoadjuvant treatment
• Measurable disease (Phase 3)/ Measurable or non-measurable evaluable disease (Safety Lead-in)
• ECOG PS 0-1
• Adequate organ function

Key Exclusion Criteria:

• Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition
• Active bacterial or viral infections in 2 weeks prior to starting dosing
• Symptomatic brain metastases