Abstract B16: NEMO: A phase 3 trial of binimetinib (MEK162) versus dacarbazine in patients with advanced NRAS-mutant melanoma who are untreated or have progressed on or after immunotherapy

Melanoma tumors often harbor mutations in the mitogen-activated protein kinase-signaling pathway family members BRAF or NRAS. NRAS mutations, observed in about 20% of patients with melanoma, are associated with higher tumor proliferation and poorer prognosis. A large retrospective analysis (n = 677) demonstrated that NRAS mutations are independently predictive of poor survival in patients with cutaneous melanoma (Jakob et al ., 2011). There are no approved targeted therapies for melanoma patients with NRAS -mutant tumors; treatments are currently limited to chemotherapy and/or immunotherapy. Binimetinib (MEK162), a potent and selective inhibitor of MEK1/2, has demonstrated promising phase 2 clinical activity in this patient subset. Here we describe the “NRAS mElanoma and MEK inhibitOr” (NEMO) trial, an ongoing 2-arm, open-label, 2:1 randomized phase 3 study designed to compare the efficacy of binimetinib vs dacarbazine in patients with metastatic NRAS -mutant melanoma (NCT01763164). Eligible patients must have advanced unresectable or metastatic cutaneous melanoma or melanoma of unknown primary origin with a documented NRAS Q61 mutation (confirmed by central laboratory molecular screening) that was previously untreated or has progressed on or after any number of immunotherapy regimens. Patients are stratified by stage, Eastern Cooperative Oncology Group performance status, and prior immunotherapy. The primary endpoint of the study is progression-free survival, and secondary endpoints include overall survival, overall response, time to response, duration of response, disease control rate, safety, and quality of life. Binimetinib is administered orally at 45 mg twice daily and dacarbazine is dosed intravenously at 1000 mg/m2 once every 3 weeks. This phase 3 trial is designed to enroll 393 patients and is currently recruiting patients at more than 150 centers across North America, South America, Europe, Asia-Pacific, and Africa. The study design, including eligibility criteria, methodology, and endpoints of the phase 3 NEMO trial will be presented. Citation Format: Georgina Long, Reinhard Dummer, Keith Flaherty, Dirk Schadendorf, Petr Arenberger, Lev Demidov, Anna Maria Di Giacomo, Mario Mandala, Giovanni Rangoni, Pascal Wolter, Naoya Yamazaki, James Ford, Ernesto Wasserman, Marine Weill, Paolo Ascierto. NEMO: A phase 3 trial of binimetinib (MEK162) versus dacarbazine in patients with advanced NRAS-mutant melanoma who are untreated or have progressed on or after immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B16.