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Clinical Trial
. 2023 Jul 20;41(21):3700-3711.
doi: 10.1200/JCO.23.00774. Epub 2023 Jun 4.

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer

Gregory J Riely  1 , Egbert F Smit  2 , Myung-Ju Ahn  3 , Enriqueta Felip  4 , Suresh S Ramalingam  5 , Anne Tsao  6 , Melissa Johnson  7 , Francesco Gelsomino  8 , Raymond Esper  9 , Ernest Nadal  10 , Michael Offin  1 , Mariano Provencio  11 , Jeffrey Clarke  12 , Maen Hussain  9 , Gregory A Otterson  13 , Ibiayi Dagogo-Jack  14 , Jonathan W Goldman  15 , Daniel Morgensztern  16 , Ann Alcasid  17 , Tiziana Usari  18 , Paul Wissel  19 , Keith Wilner  20 , Nuzhat Pathan  20 , Svitlana Tonkovyd  21 , Bruce E Johnson  22
Affiliations
Clinical Trial

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer

Gregory J Riely et al. J Clin Oncol. .

Erratum in

Abstract

Purpose: The combination of encorafenib (BRAF inhibitor) plus binimetinib (MEK inhibitor) has demonstrated clinical efficacy with an acceptable safety profile in patients with BRAFV600E/K-mutant metastatic melanoma. We evaluated the efficacy and safety of encorafenib plus binimetinib in patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC).

Methods: In this ongoing, open-label, single-arm, phase II study, patients with BRAFV600E-mutant metastatic NSCLC received oral encorafenib 450 mg once daily plus binimetinib 45 mg twice daily in 28-day cycles. The primary end point was confirmed objective response rate (ORR) by independent radiology review (IRR). Secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, time to response, and safety.

Results: At data cutoff, 98 patients (59 treatment-naïve and 39 previously treated) with BRAFV600E-mutant metastatic NSCLC received encorafenib plus binimetinib. Median duration of treatment was 9.2 months with encorafenib and 8.4 months with binimetinib. ORR by IRR was 75% (95% CI, 62 to 85) in treatment-naïve and 46% (95% CI, 30 to 63) in previously treated patients; median DOR was not estimable (NE; 95% CI, 23.1 to NE) and 16.7 months (95% CI, 7.4 to NE), respectively. DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE (95% CI, 15.7 to NE) in treatment-naïve and 9.3 months (95% CI, 6.2 to NE) in previously treated patients. The most frequent treatment-related adverse events (TRAEs) were nausea (50%), diarrhea (43%), and fatigue (32%). TRAEs led to dose reductions in 24 (24%) and permanent discontinuation of encorafenib plus binimetinib in 15 (15%) patients. One grade 5 TRAE of intracranial hemorrhage was reported. Interactive visualization of the data presented in this article is available at the PHAROS dashboard (https://clinical-trials.dimensions.ai/pharos/).

Conclusion: For patients with treatment-naïve and previously treated BRAFV600E-mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.

Trial registration: ClinicalTrials.gov NCT03915951.

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