Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer
Year: 2023
Type: article
Study design: Clinical Trial
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 (ClinicalTrials.gov identifier: NCT03915951 ), 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.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco.23.00774
Authors: Gregory J. Riely, Egbert F. Smit, Myung-Ju Ahn, Enriqueta Felip, Suresh S. Ramalingam, Anne Tsao, Melissa Johnson, Francesco Gelsomino, Raymond Esper, Ernest Nadal, Michael Offin, Mariano Provencio, Jeffrey Clarke, Maen Hussain, Gregory A. Otterson, Ibiayi Dagogo-Jack, Jonathan W. Goldman, Daniel Morgensztern, Ann Alcasid, Tiziana Usari, Paul Wissel, Keith Wilner, Nuzhat Pathan, Svitlana Tonkovyd, Bruce E. Johnson
Institutions: Memorial Sloan Kettering Cancer Center, Leiden University Medical Center, Samsung Medical Center, Sungkyunkwan University, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Winship Cancer Institute, The University of Texas MD Anderson Cancer Center, Tennessee Oncology, IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Bologna, Florida Cancer Specialists & Research Institute, Institut Català d'Oncologia, Hospital Universitario Puerta de Hierro Majadahonda, Duke Cancer Institute, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Massachusetts General Hospital, University of California, Los Angeles, Washington University in St. Louis, Pfizer (United States), Pfizer (Italy), Dana-Farber Cancer Institute
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4379278616