Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients

David M. King, Mark R. Albertini, Heidi Schalch, Jacquelyn A. Hank, Jacek Gan, Jean Surfus, David Mahvi, Joan H. Schiller, Thomas Warner, KyungMann Kim, Jens Eickhoff, Kari Kendra, Ralph Reisfeld, Stephen D. Gillies, Paul Sondel

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Purpose: To evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma. Patients and Methods: Thirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d. Results: Nineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex. Conclusion: Treatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.

Original languageEnglish (US)
Pages (from-to)4463-4473
Number of pages11
JournalJournal of Clinical Oncology
Volume22
Issue number22
DOIs
StatePublished - 2004

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Clinical Trials, Phase I
Melanoma
Maximum Tolerated Dose
Interleukin-2
human EMD 273063 antibody
Hypotension
Interleukin-2 Receptor alpha Subunit
Hypophosphatemia
Lymphocytosis
Hyperbilirubinemia
Myalgia
Arthralgia
Therapeutics
Transaminases
Intravenous Infusions
Natural Killer Cells
Hyperglycemia
Thrombocytopenia
Opioid Analgesics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

King, D. M., Albertini, M. R., Schalch, H., Hank, J. A., Gan, J., Surfus, J., ... Sondel, P. (2004). Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. Journal of Clinical Oncology, 22(22), 4463-4473. https://doi.org/10.1200/JCO.2004.11.035

Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. / King, David M.; Albertini, Mark R.; Schalch, Heidi; Hank, Jacquelyn A.; Gan, Jacek; Surfus, Jean; Mahvi, David; Schiller, Joan H.; Warner, Thomas; Kim, KyungMann; Eickhoff, Jens; Kendra, Kari; Reisfeld, Ralph; Gillies, Stephen D.; Sondel, Paul.

In: Journal of Clinical Oncology, Vol. 22, No. 22, 2004, p. 4463-4473.

Research output: Contribution to journalArticle

King, DM, Albertini, MR, Schalch, H, Hank, JA, Gan, J, Surfus, J, Mahvi, D, Schiller, JH, Warner, T, Kim, K, Eickhoff, J, Kendra, K, Reisfeld, R, Gillies, SD & Sondel, P 2004, 'Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients', Journal of Clinical Oncology, vol. 22, no. 22, pp. 4463-4473. https://doi.org/10.1200/JCO.2004.11.035
King, David M. ; Albertini, Mark R. ; Schalch, Heidi ; Hank, Jacquelyn A. ; Gan, Jacek ; Surfus, Jean ; Mahvi, David ; Schiller, Joan H. ; Warner, Thomas ; Kim, KyungMann ; Eickhoff, Jens ; Kendra, Kari ; Reisfeld, Ralph ; Gillies, Stephen D. ; Sondel, Paul. / Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 22. pp. 4463-4473.
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abstract = "Purpose: To evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma. Patients and Methods: Thirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d. Results: Nineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex. Conclusion: Treatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.",
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T1 - Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients

AU - King, David M.

AU - Albertini, Mark R.

AU - Schalch, Heidi

AU - Hank, Jacquelyn A.

AU - Gan, Jacek

AU - Surfus, Jean

AU - Mahvi, David

AU - Schiller, Joan H.

AU - Warner, Thomas

AU - Kim, KyungMann

AU - Eickhoff, Jens

AU - Kendra, Kari

AU - Reisfeld, Ralph

AU - Gillies, Stephen D.

AU - Sondel, Paul

PY - 2004

Y1 - 2004

N2 - Purpose: To evaluate the safety, toxicity, in vivo immunologic activation, and maximum-tolerated dose (MTD) of EMD 273063 (hu14.18-IL-2) in patients with metastatic melanoma. Patients and Methods: Thirty-three patients were treated with EMD 273063, a humanized anti-GD2 monoclonal antibody (mAb) linked to interleukin-2 (IL-2). EMD 273063 was given as a 4-hour intravenous infusion on days 1, 2, and 3 of week 1. Patients with stabilization or regression of disease could receive a second course of treatment at week 5. Dose levels evaluated were 0.8, 1.6, 3.2, 4.8, 6.0, and 7.5 mg/m2/d. Results: Nineteen of 33 patients completed course 1 with stable disease and went on to receive course 2. Eight patients had stable disease on completion of course 2. Grade 3 adverse events included hypophosphatemia (11 patients), hyperglycemia (three patients), hypotension (two patients), thrombocytopenia (one patient), hypoxia (three patients), elevated hepatic transaminases (two patients), and hyperbilirubinemia (one patient). Opioids were required for treatment-associated arthralgias and/or myalgias during 17 of 52 treatment courses. No grade 4 adverse events were observed. Dose-limiting toxicities at the MTD included hypoxia, hypotension, and elevations in AST/ALT. Grade 3 toxicities were anticipated based on prior studies of IL-2 or anti-GD2 mAbs, and all resolved. Immune activation was induced, as measured by lymphocytosis, increased peripheral-blood natural killer activity, and cell numbers, and increased serum levels of the soluble alpha chain of the IL-2 receptor complex. Conclusion: Treatment with the immunocytokine EMD 273063 induced immune activation and was associated with reversible clinical toxicities at the MTD of 7.5 mg/m2/d in melanoma patients.

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