Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients with Metastatic Melanoma
نویسندگان
چکیده
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 (188)Re-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 (188)Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of (188)Re-6D2 was escalated to 54 mCi. SPECT/CT revealed (188)Re-6D2 uptake in melanoma metastases. The mean effective half-life of (188)Re-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 (188)Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.
منابع مشابه
Pre-clinical evaluation and efficacy studies of a melanin-binding IgM antibody labeled with 188Re against experimental human metastatic melanoma in nude mice.
PURPOSE Currently there is no satisfactory treatment for metastatic melanoma. Radioimmunotherapy (RIT) uses the antigen-antibody interaction to deliver lethal radiation to target cells. Recently we established the feasibility of targeting melanin in tumors with 188-Rhenium ((188)Re)-labeled 6D2 mAb to melanin. Here we carried out pre-clinical development of (188)Re-6D2 to accrue information nec...
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متن کاملClinical Study Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients withMetastatic Melanoma
Hadassah Medical Center, Hebrew University, Kiryat Hadassah, 91120 Jerusalem, Israel 2 Chaim Sheba Medical Center, Tel Hashomer, 52621 Ramat Gan, Israel 3 Sackler Faculty of Medicine, Tel Aviv Medical Center, 69978 Tel Aviv, Israel 4 Rambam Health Care Campus, 31096 Haifa, Israel 5 Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA 6 Pain erapeutics, Inc., Austi...
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ورودعنوان ژورنال:
دوره 2013 شماره
صفحات -
تاریخ انتشار 2013