Case report: response to the ERK1/2 inhibitor ulixertinib in BRAF D594G cutaneous melanoma

Melanoma Res. 2022 Aug 1;32(4):295-298. doi: 10.1097/CMR.0000000000000830. Epub 2022 May 12.


Melanoma is characterized by oncogenic mutations in pathways regulating cell growth, proliferation, and metabolism. Greater than 80% of primary melanoma cases harbor aberrant activation of the mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway, with oncogenic mutations in BRAF, most notably BRAF V600E, being the most common. Significant progress has been made in BRAF-mutant melanoma using BRAF and MEK inhibitors; however, non-V600 BRAF mutations remain a challenge with limited treatment options. We report the case of an individual diagnosed with stage III BRAF D594G-mutant melanoma who experienced an extraordinary response to the ERK1/2 inhibitor ulixertinib as fourth-line therapy. Ulixertinib was obtained via an intermediate expanded access protocol with unique flexibility to permit both single-agent and combination treatments, dose adjustments, breaks in treatment to undergo surgery, and long-term preventive treatment following surgical resection offering this patient the potential for curative treatment.

Publication types

  • Case Reports

MeSH terms

  • Aminopyridines
  • Cell Line, Tumor
  • Humans
  • MAP Kinase Signaling System
  • Melanoma* / genetics
  • Melanoma, Cutaneous Malignant
  • Mitogen-Activated Protein Kinase Kinases
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins B-raf
  • Pyrroles
  • Skin Neoplasms* / drug therapy


  • Aminopyridines
  • Protein Kinase Inhibitors
  • Pyrroles
  • ulixertinib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinase Kinases