Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

BMC Cancer. 2011 Dec 13;11:515. doi: 10.1186/1471-2407-11-515.


Background: We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4(+)CD25(HI)Foxp3(+) regulatory T cells and expanded melanoma-specific CD8(+) T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.

Methods: In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[(18)F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.

Results: After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; p value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.

Conclusions: These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.

Trial registration: NCT00299689.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Diphtheria Toxin / therapeutic use*
  • Female
  • Humans
  • Interleukin-2 / therapeutic use*
  • Kentucky
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Positron-Emission Tomography
  • Recombinant Fusion Proteins / therapeutic use
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Survival Analysis
  • T-Lymphocytes
  • Tomography, X-Ray Computed


  • Antineoplastic Agents
  • Diphtheria Toxin
  • Interleukin-2
  • Recombinant Fusion Proteins
  • denileukin diftitox

Associated data