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

Riely, G.J.; Ahn, M.J.; Clarke, J.M.; Dagogo-Jack, I.; Esper, R.; Felip, E.; Gelsomino, F.; Goldman, J.W.; Hussein, M.; Johnson, M.; Marrone, K.A.; Morgensztern, D.; Nadal, E.; Negrao, M.; Offin, M.; Provencio, M.; Ramalingam, S.S.; Roof, L.; Sanborn, R.E.; Smit, E.F.; Tsao, A.; Usari, T.; Alcasid, A.; Wilner, K.; Tonkovyd, S.; Zhang, X.S.; Johnson, B.E.

doi:doi:10.1016/j.jtho.2025.05.023

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. Methods: 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. Results: 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...Show moreIntroduction: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical Trial Information: ClinicalTrials.gov Identifier: NCT03915951 (c) 2025 The Authors. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Show less

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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