Originally published as JCO Early Release 10.1200/JCO.2006.07.8972 on May 21 2007

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Phase I/II Study of an Anti-CD30 Monoclonal Antibody (MDX-060) in Hodgkin's Lymphoma and Anaplastic Large-Cell Lymphoma

Stephen M. Ansell, Steven M. Horwitz, Andreas Engert, Khuda Dad Khan, Thomas Lin, Roger Strair, Tibor Keler, Robert Graziano, Diann Blanset, Michael Yellin, Steven Fischkoff, Albert Assad, Peter Borchmann

From the Mayo Clinic School of Medicine, Rochester, MN; Memorial Sloan-Kettering Cancer Center, New York, NY; University of Cologne, Cologne, Germany; American Health Network Oncology, Indianapolis, IN; Ohio State University, Columbus, OH; University of Medicine and Dentistry of New Jersey, Newark; and Medarex Inc, Princeton, NJ

Address reprint requests to Stephen M. Ansell, MD, PhD, Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: ansell.stephen{at}mayo.edu

Purpose: MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1 monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed.

Patients and Methods: In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients—16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma—were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg.

Results: MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment.

Conclusion: MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.

published online ahead of print at www.jco.org on May 21, 2007.

S.M.A. and S.M.H. contributed equally to this work.

Presented in part at the 45th Annual Meeting of the American Society of Hematology, December 6-9, 2003, San Diego, CA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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