Encorafenib, Binimetinib and Cetuximab in Subjects With Previously Untreated BRAF-mutant ColoRectal Cancer

Status: Active

Description

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 and confirmed by central laboratory
  • Evidence of measurable disease as per RECIST, v1.1
  • Subject able to receive cetuximab as per approved label with regards to RAS status
  • ECOG Status 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

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available

Colorado

Denver
University of Colorado
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Asha Rose Krishnan
Phone: 646-888-1378
Email: krishna2@mskcc.org

Trial Objectives and Outline

The presence of a BRAFV600E mutation is considered a marker of poor prognosis in subjects with mCRC. The preclinical results and preliminary clinical data together justify the evaluation of this triple combination in the first-line setting of this population. The primary objective of the study is to evaluate the antitumor activity of the combination of encorafenib, binimetinib and cetuximab by assessing the overall response rate in adult subjects with previously untreated BRAFV600E-mutant metastatic colorectal cancer. It will also assess the effect of the triple combination on the duration of response, time to response, progression-free survival and overall survival and assess the effect on quality of life. It will also characterize the safety and tolerability of the triple combination as well as describe the pharmacokinetics (PK) of encorafenib, binimetinib, and cetuximab.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Pierre Fabre Medicament

Trial IDs

Primary ID W00090 GE 2 01
Secondary IDs NCI-2019-01290
Clinicaltrials.gov ID NCT03693170