Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design

Future Oncol. 2022 Mar;18(7):781-791. doi: 10.2217/fon-2021-1250. Epub 2021 Dec 17.


BRAFV600 oncogenic driver mutations occur in 1-2% of non-small-cell lung cancers (NSCLCs) and have been shown to be a clinically relevant target. Preclinical/clinical evidence support the efficacy and safety of BRAF and MEK inhibitor combinations in patients with NSCLC with these mutations. We describe the design of PHAROS, an ongoing, open-label, single-arm, phase II trial evaluating the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with metastatic BRAFV600-mutant NSCLC, as first- or second-line treatment. The primary end point is objective response rate, based on independent radiologic review (per RECIST v1.1); secondary objectives evaluated additional efficacy end points and safety. Results from PHAROS will describe the antitumor activity/safety of encorafenib plus binimetinib in patients with metastatic BRAFV600-mutant NSCLC.

Trial registration: ClinicalTrials.gov NCT03915951.

Keywords: BRAFV600 mutation; binimetinib; clinical trial; efficacy; encorafenib; non-small-cell lung cancer; objective response rate; safety.

Plain language summary

Plain language summary Some people with non-small-cell lung cancer (NSCLC) have changes in a gene called BRAF (known as ‘gene mutations’). One common BRAF mutation is called ‘V600’. Combinations of medicines that block proteins encoded by mutant BRAF and another gene called MEK can shrink tumors and slow their progression. We describe the design of PHAROS, a clinical trial investigating encorafenib (mutant BRAF inhibitor) combined with binimetinib (MEK inhibitor) in people with BRAFV600-mutant NSCLC that had spread to other parts of the body (‘metastatic disease’). People are monitored for side effects and to see if their tumor shrunk. PHAROS includes people treated with encorafenib plus binimetinib as their first treatment for metastatic disease, and people whose cancer progressed after previous anticancer therapy. Clinical trial registration: Clinicaltrials.gov (NCT03915951) and EudraCT (2019-000417-37).

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Carbamates / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sulfonamides / administration & dosage


  • Benzimidazoles
  • Carbamates
  • Sulfonamides
  • binimetinib
  • encorafenib
  • Proto-Oncogene Proteins B-raf

Associated data

  • ClinicalTrials.gov/NCT03915951

Grant support