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

Author(s): Gregory J. Riely, MD, PhD¹; Egbert F. Smit, MD, PhD²; Myung-Ju Ahn, MD, PhD³; Enriqueta Felip, MD, PhD⁴; Suresh S. Ramalingam, MD⁵; Anne Tsao, MD⁶; Melissa Johnson, MD⁷; Francesco Gelsomino, MD⁸; Raymond Esper, MD, PhD⁹; Ernest Nadal, MD, PhD10; Michael Offin, MD¹; Mariano Provencio, MD, PhD¹¹; Jeffrey Clarke, MD¹²; Maen Hussain, MD⁹; Gregory A. Otterson, MD¹³; Ibiayi Dagogo-Jack, MD¹⁴; Jonathan W. Goldman, MD¹⁵; Daniel Morgensztern, MD¹⁶; Ann Alcasid, BA¹⁷; Tiziana Usari, BSc¹⁸; Paul Wissel, MD¹⁹; Keith Wilner, PhD²⁰; Nuzhat Pathan, PhD²⁰; Svitlana Tonkovyd, MD²¹; and Bruce E. Johnson, MD²²

Source: DOI: 10.1200/JCO.23.00774 Journal of Clinical Oncology 41, no. 21 (July 20, 2023) 3700-3711.

Dr. Maen Hussein's Thoughts

Targeted therapy in NSCLC, FCS was part of this trial.

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.

Author Affiliations

¹Memorial Sloan Kettering Cancer Center, New York, NY;²Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, the Netherlands;³Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;⁴Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain;⁵Winship Cancer Institute of Emory University, Atlanta, GA;⁶MD Anderson Cancer Center, Houston, TX;⁷Tennessee Oncology, Sarah Cannon Research Institute, Nashville, TN;⁸Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;⁹Florida Cancer Specialists, Fort Myers, FL;¹⁰Medical Oncology, Catalan Institute of Oncology, Barcelona, Spain;¹¹Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain;¹²Duke Cancer Center, Durham, NC;¹³Ohio State University Comprehensive Cancer Center, Columbus, OH;¹⁴Massachusetts General Hospital, Boston, MA;¹⁵David Geffen School of Medicine at UCLA, Los Angeles, CA;¹⁶Washington University School of Medicine, St Louis, MO;¹⁷Pfizer, Collegeville, PA;¹⁸Pfizer, Milan, Italy;¹⁹Pfizer, New York, NY;²⁰Pfizer, La Jolla, CA;²¹Pfizer, Warsaw, Poland;²²Dana-Farber Cancer Institute, Boston, MA

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