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Journal of Skin Cancer
Volume 2013 (2013), Article ID 828329, 8 pages
http://dx.doi.org/10.1155/2013/828329
Clinical Study

Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients with Metastatic Melanoma

M. Klein,1 M. Lotem,1 T. Peretz,1 S. T. Zwas,2 S. Mizrachi,1 Y. Liberman,1 R. Chisin,1 J. Schachter,2 I. G. Ron,3 G. Iosilevsky,4 J. A. Kennedy,4 E. Revskaya,5 A. W. de Kater,6 E. Banaga,6 V. Klutzaritz,6 N. Friedmann,6 E. Galun,1 G. L. DeNardo,7 S. J. DeNardo,7 A. Casadevall,5 E. Dadachova,5 and G. B. Thornton6

1Hadassah Medical Center, Hebrew University, Kiryat Hadassah, 91120 Jerusalem, Israel
2Chaim Sheba Medical Center, Tel Hashomer, 52621 Ramat Gan, Israel
3Sackler Faculty of Medicine, Tel Aviv Medical Center, 69978 Tel Aviv, Israel
4Rambam Health Care Campus, 31096 Haifa, Israel
5Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
6Pain Therapeutics, Inc., Austin, TX 78731, USA
7Davis Medical Center, University of California, Sacramento, CA 95817, USA

Received 13 July 2012; Accepted 10 December 2012

Academic Editor: Silvia Moretti

Copyright © 2013 M. Klein et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

There is a need for effective “broad spectrum” therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of 188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM) patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi 188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of 188Re-6D2 was escalated to 54 mCi. SPECT/CT revealed 188Re-6D2 uptake in melanoma metastases. The mean effective half-life of 188Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.