{"entity":{"id":"paper-pharos-j-thorac-oncol-2025","kind":"paper","name":"Updated Efficacy and Safety From the Phase 2 PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic NSCLC-A Brief Report","aka":[],"tldr":"Published report from the PHAROS trial registered as NCT03915951, in Journal of Thoracic Oncology (2025), chosen as the most cited paper whose own text cites the registry id.","summary":"Introduction: The PHAROS primary analysis revealed robust antitumor activity and acceptable safety with encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC (mNSCLC). We report results after 18 months of additional follow-up.\n\nMethods: In this ongoing open-label, single-arm, phase 2 study, patients with BRAF V600E-mutant mNSCLC (59 treatment-naive and 39 previously treated) received encorafenib 450 mg once daily and binimetinib 45 mg twice daily. Primary end point was objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.\n\nResults: At this data cutoff, median treatment duration with encorafenib plus binimetinib was 16.3 months in treatment-naive and 5.5 months in previously treated patients; minimum follow-up was approximately 32 and 22 months, respectively. In treatment-naive patients, the ORR was 75%, median DOR was 40.0 months, median PFS was 30.2 months, median OS was not estimable (95% confidence interval: 31.3-not estimable), and the 3-year OS probability was 53%. In previously treated patients, the ORR was 46%, median DOR was 16.7 months, median PFS was 9.3 months, median OS was 22.7 months, and the 3-year OS probability was 29%. Overall, the most frequent treatment-related adverse events were nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%). Treatment-related adverse events led to dose reductions and permanent treatment discontinuations in 25 (26%) and 16 (16%) patients, respectively.\n\nConclusions: With longer follow-up, encorafenib plus binimetinib showed durable and clinically meaningful antitumor activity, especially in treatment-naive patients, with a manageable safety profile in patients with BRAF V600E-mutant mNSCLC.\n\nClinical trial information: ClinicalTrials.gov Identifier: NCT03915951.\n\nIndexed on Europe PMC as PubMed record 40480428 (DOI 10.1016/j.jtho.2025.05.023). Its abstract cites the registry id NCT03915951, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"J Thorac Oncol 2025","url":"https://doi.org/10.1016/j.jtho.2025.05.023"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/40480428/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/40480428"},{"label":"ClinicalTrials.gov NCT03915951","url":"https://clinicaltrials.gov/study/NCT03915951"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["pharos"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["journal-of-thoracic-oncology"],"dependsOn":[],"notes":[],"journal":"Journal of Thoracic Oncology","year":2025,"doi":"10.1016/j.jtho.2025.05.023","pmid":"40480428","authors":"Riely GJ, Ahn MJ, Clarke JM, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT03915951 with the most citations, so it is the natural first reading for anyone following the PHAROS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-pharos-j-thorac-oncol-2025/","neighbours":{"trial":[{"id":"pharos","kind":"trial","name":"PHAROS","route":"/trials/pharos/"}],"journal":[{"id":"journal-of-thoracic-oncology","kind":"journal","name":"Journal of Thoracic Oncology","route":"/journals/journal-of-thoracic-oncology/"}]}}