Phase I Clinical Trial of the Immunocytokine EMD 273063 in Melanoma Patients

• Published in: Journal of clinical oncology Vol. 22; no. 22; pp. 4463 - 4473
• Main Authors: KING, David M, ALBERTINI, Mark R, EICKHOFF, Jens, KENDRA, Kari, REISFELD, Ralph, GILLIES, Stephen D, SONDEL, Paul, SCHALCH, Heidi, HANK, Jacquelyn A, GAN, Jacek, SURFUS, Jean, MAHVI, David, SCHILLER, Joan H, WARNER, Thomas, KIM, Kyungmann
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15-11-2004; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Dermatology; Female; Humans; Infusions, Intravenous; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Interleukin-2 - therapeutic use; Male; Maximum Tolerated Dose; Medical sciences; Melanoma - drug therapy; Middle Aged; Skin Neoplasms - drug therapy; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Human; Phase I trial; Cancerology; Malignant tumor; Malignant melanoma
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.11.035

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.
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.
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.
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.