Clinical Trials

Inclusion Criteria:

• SLI:
  • Male or female participants age ≥ 18 years at the time of informed consent.
• Phase 3:
  • Male or female participants age ≥ 16 years at the time of informed consent/assent. 
• Body weight ≥ 40 kg.
• Participants with histologically or cytologically confirmed colorectal adenocarcinoma.
• Participants with evidence of metastatic disease.
• Able to provide a sufficient amount of representative tumor specimen for central testing of BRAF V600E mutation status.
  • Note: Tumor sample must be in an FFPE block, newly collected fixed biopsy sample, or a minimum of 15 unstained slides of analyzable tissue. Participants with fewer than 15 slides of analyzable tissue may be considered eligible if the Sponsor determines that the slides are sufficient for central testing of BRAF V600E mutation status.
• Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
  • Note: Participants ≥ 16 years old that are under guardianship may participate with the consent of their legally authorized guardian if permitted by local regulations. When appropriate, adolescent participants will be included in all discussions.

Exclusion Criteria:

• SLI:
  • Prior systemic regimen containing both oxaliplatin and irinotecan (e.g., FOLFOXIRI).
• Previous treatment with any selective BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib, XL281/BMS-908662) or any EGFR inhibitor (eg, cetuximab, panitumumab) prior to screening.
• Use of any prohibited medication (including herbal medication), supplement or food that is a moderate or strong inhibitor or inducer of CYP3A4/5 ≤ 1 week prior to the start of study intervention.
• Major surgery (eg, inpatient procedure with regional or general anesthesia) or completion of radiation therapy ≤ 4 weeks prior to randomization.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
• Has met any of the Molecular Prescreening exclusion criteria.
• Has documented clinical disease progression (e.g., worsening of performance status, clinical symptoms, or clinically significant laboratory parameters demonstrating worsening of disease) or radiographic disease progression during the Screening period.
• Symptomatic brain metastasis.
  • Note: Participants previously treated or untreated for this condition who are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed. Brain metastases must be stable for ≥4 weeks prior to randomization.
• Known contraindication to receiving cetuximab including hypersensitivity or toxicity that would suggest an inability to tolerate maximum cetuximab dose of 500 mg/m^2 .
• Known sensitivity or contraindication to any component of study intervention or their excipients at the planned doses.
• Known contraindication to receive any component of the Control Arm at the planned doses; refer to the most recent local label, as applicable.
• Pregnant, confirmed by a positive β-hCG laboratory test result, or is breastfeeding (lactating).