Nilotinib in patients with metastatic melanoma harboring KIT gene aberration

Invest New Drugs. 2012 Oct;30(5):2008-14. doi: 10.1007/s10637-011-9763-9. Epub 2011 Nov 9.


Purpose: Patients with metastatic melanoma have a poor prognosis and few treatment options are available. We evaluated the anti-tumor activity and safety of nilotinib, a KIT inhibitor, in patients with metastatic melanoma harboring KIT alterations, either mutations or amplifications.

Patients and methods: This study was open-label, single center, prospective phase II clinical trial. Between October 2009 and April 2011, 11 patients with metastatic melanoma harboring KIT gene mutations or KIT gene amplifications were enrolled in the first stage of phase II study and nilotinib was administered orally at a dose of 400 mg twice a day until disease progression or intolerable toxicities. The primary endpoint was response rate and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).

Results: Of 11 patients, 9 patients were evaluable for treatment response. Of 9 patients, three patients had KIT mutations in exon 11, Leu576Pro, Val559Ala and Lys558Arg; and 6 patients had KIT amplifications > 50 copies compared to control DNA. Two patients achieved partial response (22.2%) and 5 patients achieved stable disease (55.6%). In two patients who responded to nilotinib, both had KIT mutations and showed durable response for 8.4 months and 10.0+ months. Of note, one patient with KIT amplification had stable disease with response for 6 months. A decrease in tumor size from baseline was observed in four patients (44.4%). Nilotinib 800 mg/d was very well tolerated with grade 1 nausea and grade 1 dry-eye being the most common adverse events.

Conclusions: We have decided to publish the preliminary results because anti-tumor activity of nilotinib was promising in KIT mutated patients. Although our results are preliminary, nilotinib had very favorable toxicity profile with durable response in metastatic melanoma patients with KIT mutations. The anti-tumor activity of nilotinib in melanoma patients with KIT amplification is yet to be determined in future studies. Currently, phase II nilotinib trial is ongoing in Korea as multi-center study.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Amplification
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / enzymology
  • Melanoma / genetics
  • Middle Aged
  • Mutation*
  • Prospective Studies
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*


  • Antineoplastic Agents
  • Pyrimidines
  • Proto-Oncogene Proteins c-kit
  • nilotinib