PHAROS Study Design

This segment reviews the design and patient characteristics of the PHAROS study, a phase II trial evaluating the BRAF-MEK inhibitor combination encorafenib and binimetinib in patients with BRAF V600E-mutant metastatic NSCLC. PHAROS enrolled two cohorts: 59 treatment-naïve patients and 39 patients who had received one prior line of therapy, most commonly chemotherapy, immunotherapy, or a combination. All patients received standard-dose encorafenib and binimetinib, with treatment continued until disease progression. The primary endpoint was objective response rate assessed by independent radiologic review, with additional key outcomes including progression-free survival (PFS), overall survival (OS), and safety, some of which were presented at recent meetings such as ESMO.

Eligibility criteria were typical for targeted therapy trials. Patients were required to have confirmed BRAF V600E mutations and could be either untreated or have received no more than one prior systemic therapy in the advanced setting. Prior BRAF or MEK inhibitor therapy was not allowed. Patients with central nervous system metastases were eligible if asymptomatic, whereas those with symptomatic CNS disease or concurrent actionable oncogenic drivers were excluded.

Baseline characteristics reflected a typical BRAF V600E NSCLC population: median age around 70 years, a majority with a smoking history but a substantial never-smoker subgroup, and relatively low rates of baseline CNS involvement. Prior treatments varied, underscoring ongoing heterogeneity in frontline management for this population.