Originally published as JCO Early Release 10.1200/JCO.2008.16.1927 on November 17 2008

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Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma

Jeffrey S. Weber, Steven O’Day, Walter Urba, John Powderly, Geoff Nichol, Michael Yellin, Jolie Snively, Evan Hersh

From the University of Southern California/Norris Comprehensive Cancer Center; The Angeles Clinic and Research Institute, Los Angeles, CA; Robert Franz Cancer Center, Earle A. Chiles Research Institute, Portland, OR; the University of Arizona Cancer Center, Tucson, AZ; Carolina Bio-Oncology Institute, Huntersville, NC; and Medarex, Inc, Annadale, NJ

Corresponding author: Jeffrey Weber, MD, PhD, H Lee Moffitt Cancer Center, 12902 Magnolia Dr, SRB-2, Tampa, FL 33612; e-mail: jeffrey.weber{at}moffitt.org

Purpose The primary objective of this phase I/II study was to determine the safety and pharmacokinetic profile of either transfectoma- or a hybridoma-derived ipilimumab. Secondary objectives included determination of a maximum-tolerated dose and assessment of clinical activity.

Patients and Methods Eighty-eight patients with unresectable stage III or IV melanoma with at least one measurable lesion were treated. Mean age was 59 years, with 65% male and 35% female patients, and 79% of patients had received prior systemic therapy. Single doses of ipilimumab up to 20 mg/kg (group A, single dose), multiple doses up to 5 mg/kg (group A, multiple dose), and multiple doses up to 10 mg/kg (group B) were administered.

Results Single dosing up to 20 mg/kg of transfectoma antibody was well tolerated, as were multiple doses up to 10 mg/kg without a maximum-tolerated dose. In group B, dose-limiting toxicity was seen in six of 23 melanoma patients. Grade 3 or 4 immune-related adverse events (irAEs) were observed in 14% of patients (12 of 88 patients), and grade 1 or 2 irAEs were seen in an additional 58%. The half-life of ipilimumab was 359 hours. In group B, there was one partial response (23+ months), one complete response (21+ months), and seven patients with stable disease (SD), for a disease control rate of 39%. Two patients in group B with SD had slow, steady decline in tumor burden that was ongoing at 1 year of observation.

Conclusion Ipilimumab has activity in patients with metastatic melanoma. Late responses were observed in patients with prolonged SD.

published online ahead of print at www.jco.org on November 17, 2008.

Presented in part as a poster discussion at the 43rd Annual Meeting of the American Society for Clinical Oncology, June 1-5, 2007, Chicago, IL.

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

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