Phase IB trial for malignant melanoma using R24 monoclonal antibody, interleukin-2/alpha-interferon

Med Oncol. 1998 Sep;15(3):191-8. doi: 10.1007/BF02821938.


The inflammatory tumor lymphocytic infiltrates and spontaneous tumor regressions seen in patients with metastatic malignant melanomas suggest a cellular immune involvement. Enhancement of such responses has been the goal of R24 (GD3 ganglioside-specific) monoclonal antibody trials, alone and in combination with other agents. This study reports the results of 21 patients treated in a phase IB trial employing R24 (0, 5, 25, 50 mg/m2) administered by continuous i.v. infusion on days 1-5 followed by 3 MU each of interleukin-2 (IL-2) and alpha interferon (alpha-IFN) given subcutaneously on days 8-12, 15-19 and 22-26. R24-related toxicities occurred pre-dominantly at the 25 and 50 mg/m2 doses. One patient (50 mg/m2 R24) exhibited a dose-limiting Grade 4 anaphylaxis. Cytokine-related toxicities required IL-2/alpha-IFN dose reduction in two patients and early termination of treatment in five additional patients. Nine of 20 baseline biopsies showed chronic inflammation; six with lymphocytic tumor infiltration and three where inflammation was confined to the perivascular/peritumoral spaces. No day 8 or 29 biopsies in the R24-treated groups demonstrated treatment-induced tumor lymphocytic infiltrates. However, one patient randomized to no R24 treatment, showed a significant inflammatory tumor lymphocytic infiltration at days 8 and 29. Eighteen of 21 treated patients were evaluable for response. One (5%) patient receiving IL-2/alpha-IFN alone had stable disease lasting 1.5 years. Five (28%) R24, IL-2/alpha-IFN-treated patients had stable disease ranging from 6 to 32 weeks, with one patient remaining alive 2.5 years post-treatment. Although this combined treatment program was generally well tolerated, no objective responses were seen and significant R24-induced tumor lymphocytic infiltrates were not demonstrated.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Flow Cytometry
  • Gangliosides / immunology*
  • Humans
  • Immunohistochemistry
  • Immunophenotyping
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / pathology
  • Middle Aged
  • T-Lymphocytes


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Gangliosides
  • Interferon-alpha
  • Interleukin-2
  • ganglioside, GD3