Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer
Condition: BRAF V600E-mutant Metastatic Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: encorafenib; Binimetinib; Cetuximab
Intervention description: 300 mg administered orally once daily (QD); Binimetinib 45 mg administered orally twice daily (BID); Standard of care for the 28 first weeks(*) and then every 2 weeks (**) :
(*) 400 mg/m2 administered as a 120-min infusion on Cycle 1 Day 1, followed by 250 mg/m2 administered as a 60-min infusion once weekly (QW) for the first 28 weeks. (**) 500 mg/m2 administered as a 120-min infusion twice weekly (Q2W) from Week 29 (Cycle 8 Day 1) onward.
Following implementation of an Urgent Safety Measure on 26 Mar 2020 due to the outbreak of COVID-19 pandemic, cetuximab infusions could be administered Q2W regardless of the cycle number, after investigator's evaluation of the benefit/risk ratio for the subject, with regards to COVID-19 pandemic.
Intervention MeSH terms: Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Masking description: All involved know the identity of the intervention assignment.
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Colorectal Cancer

Summary:

      The purpose of this study is to evaluate the efficacy and safety of the combination of study
      drugs encorafenib, binimetinib and cetuximab in patients who have BRAF V600 mutant metastatic
      colorectal cancer and have not received any prior treatment for their metastatic disease.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female ≥ 18 years of age

          -  Histologically or cytologically confirmed CRC that is metastatic

          -  Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to
             screening

          -  Evidence of measurable disease as per RECIST, v1.1

          -  Subject able to receive cetuximab as per approved label with regards to RAS status

          -  Eastern Cooperative Oncology Group Status (ECOG) 0 or 1

          -  Adequate renal, hepatic, cardiac and bone marrow functions and adequate electrolytes
             as per protocol

          -  Subject able to take oral medications

        Exclusion Criteria:

          -  Prior systemic therapy for metastatic disease

          -  Prior treatment with any RAF inhibitor, MEK inhibitor, cetuximab or other anti-EGFR
             inhibitors

          -  Symptomatic brain metastasis or Leptomeningeal disease

          -  History or current evidence of Retinal Vein Occlusion (RVO) or current risk factors
             for RVO

          -  History of chronic inflammatory bowel disease or Crohn's disease requiring medical
             intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12
             months prior to first dose.

          -  Impaired cardiovascular function or clinically significant cardiovascular diseases:
             history of myocardial infarction or coronary disorders within 6 months prior to start
             of study treatment, symptomatic congestive heart failure (grade 2 or higher), past or
             current clinically significant arrhythmia and/or conduction disorder within 6 months
             prior to study treatment start

          -  History of thromboembolic or cerebrovascular events within 6 months prior to start of
             study treatment

          -  Concurrent neuromuscular disorder that is associated with potential elevation of
             Creatine Kinase

          -  Known contraindication to cetuximab administration as per SPC/approved label