Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients

Mark R. Albertini, Jacquelyn A. Hank, Joan H. Schiller, Masoud Khorsand, Agnes A. Borchert, Jacek Gan, Robin Bechhofer, Barry Storer, Ralph A. Reisfeld, Paul M. Sondel

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

We conducted a Phase IB trial of antidisialoganglioside chimeric 14.18 (ch14.18) antibody and interleukin 2 (IL-2) to determine the maximal tolerated dose (MTD), immunological effects, antitumor effects, and toxicity of this treatment combination. Twenty-four melanoma patients received immunotherapy with ch14.18 antibody and a continuous infusion of Roche IL-2 (1.5 x 106 units/m2/day) given 4 days/week for 3 weeks. The ch14.18 antibody (dose level, 2-10 mg/m2/day) was scheduled to be given for 5 days, before, during, or following initial systemic IL-2 treatment. The ch14.18 MTD was 7.5 mg/m2/day, and 15 patients were treated with the ch14.18 MTD. Immunological effects included the induction of lymphokine-activated killer activity and antibody-dependent cellular cytotoxicity by peripheral blood mononuclear cells. In addition, serum samples obtained following ch14.18 infusions were able to facilitate in vitro antibody-dependent cellular cytotoxicity. Antitumor activity included one complete response, one partial response, eight patients with stable disease, and one patient with >50% decrease of hepatic metastases in the face of recurrence of a s.c. lesion. Dose-limiting toxicities were a severe allergic reaction and weakness, pericardial effusion, and decreased performance status. Most patients treated at the MTD had abdominal, chest, or extremity pain requiring i.v. morphine. One patient had an objective peripheral neuropathy. This IL-2 and ch14.18 treatment combination induces immune activation in all patients and antitumor activity in some melanoma patients. We are attempting to enhance this treatment approach by addition of the anti-GD3 R24 antibody to this IL-2 and ch14.18 regimen.

Original languageEnglish (US)
Pages (from-to)1277-1288
Number of pages12
JournalClinical Cancer Research
Volume3
Issue number8
StatePublished - Aug 1 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Albertini, M. R., Hank, J. A., Schiller, J. H., Khorsand, M., Borchert, A. A., Gan, J., Bechhofer, R., Storer, B., Reisfeld, R. A., & Sondel, P. M. (1997). Phase IB trial of chimeric antidisialoganglioside antibody plus interleukin 2 for melanoma patients. Clinical Cancer Research, 3(8), 1277-1288.