Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial

Reinhard Dummer, Dirk Schadendorf, Paolo A Ascierto, Ana Arance, Caroline Dutriaux, Anna Maria Di Giacomo, Piotr Rutkowski, Michele Del Vecchio, Ralf Gutzmer, Mario Mandala, Luc Thomas, Lev Demidov, Claus Garbe, David Hogg, Gabriella Liszkay, Paola Queirolo, Ernesto Wasserman, James Ford, Marine Weill, L Andres SirulnikValentine Jehl, Viviana Bozón, Georgina V Long, Keith Flaherty

Research output: Contribution to journalArticlepeer-review


BACKGROUND: There are no established therapies specific for NRAS-mutant melanoma despite the emergence of immunotherapy. We aimed to assess the efficacy and safety of the MEK inhibitor binimetinib versus that of dacarbazine in patients with advanced NRAS-mutant melanoma.

METHODS: NEMO is an ongoing, randomised, open-label phase 3 study done at 118 hospitals in 26 countries. Patients with advanced, unresectable, American Joint Committee on Cancer stage IIIC or stage IV NRAS-mutant melanoma who were previously untreated or had progressed on or after previous immunotherapy were randomised (2:1) to receive either binimetinib 45 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Randomisation was stratified by stage, performance status, and previous immunotherapy. The primary endpoint was progression-free survival assessed by blinded central review in the intention-to-treat population. Safety analyses were done in the safety population, consisting of all patients who received at least one study drug dose and one post-baseline safety assessment. This study is registered with, number NCT01763164 and with EudraCT, number 2012-003593-51.

FINDINGS: Between Aug 19, 2013, and April 28, 2015, 402 patients were enrolled and randomly assigned, 269 to binimetinib and 133 to dacarbazine. Median follow-up was 1·7 months (IQR 1·4-4·1). Median progression-free survival was 2·8 months (95% CI 2·8-3·6) in the binimetinib group and 1·5 months (1·5-1·7) in the dacarbazine group (hazard ratio 0·62 [95% CI 0·47-0·80]; one-sided p<0·001). Grade 3-4 adverse events seen in at least 5% of patients the safety population in either group were increased creatine phosphokinase (52 [19%] of 269 patients in the binimetinib group vs none of 114 in the dacarbazine group), hypertension (20 [7%] vs two [2%]), anaemia (five [2%] vs six [5%]), and neutropenia (two [1%] vs ten [9%]). Serious adverse events (all grades) occurred in 91 (34%) patients in the binimetinib group and 25 (22%) patients in the dacarbazine group.

INTERPRETATION: Binimetinib improved progression-free survival compared with dacarbazine and was tolerable. Binimetinib might represent a new treatment option for patients with NRAS-mutant melanoma after failure of immunotherapy.

FUNDING: Array BioPharma and Novartis Pharmaceuticals Corporation.

Original languageEnglish
Pages (from-to)435-445
Number of pages11
JournalThe Lancet Oncology
Issue number4
Publication statusPublished - Apr 2017


  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Benzimidazoles
  • Dacarbazine
  • Female
  • Follow-Up Studies
  • GTP Phosphohydrolases
  • Humans
  • Male
  • Melanoma
  • Membrane Proteins
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Prognosis
  • Survival Rate
  • Clinical Trial, Phase III
  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial


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