Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma

M Klein; M Lotem; T Peretz; S T Zwas; S Mizrachi; Y Liberman; R Chisin; J Schachter; I G Ron; G Iosilevsky; J A Kennedy; E Revskaya; A W de Kater; E Banaga; V Klutzaritz; N Friedmann; E Galun; G L Denardo; S J Denardo; A Casadevall; E Dadachova; G B Thornton

doi:10.1155/2013/828329

Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma

M Klein, M Lotem, T Peretz, S T Zwas, S Mizrachi, Y Liberman, R Chisin, J Schachter, I G Ron, G Iosilevsky, J A Kennedy, E Revskaya, A W de Kater, E Banaga, V Klutzaritz, N Friedmann, E Galun, G L Denardo, S J Denardo, A CasadevallE Dadachova, G B Thornton

Institute for Medical Research Israel-Canada (IMRIC)

Research output: Contribution to journal › Article › peer-review

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 (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.

Original language	English
Pages (from-to)	828329
Journal	Journal of Skin Cancer
Volume	2013
DOIs	https://doi.org/10.1155/2013/828329
State	Published - 2013

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Klein, M., Lotem, M., Peretz, T., Zwas, S. T., Mizrachi, S., Liberman, Y., Chisin, R., Schachter, J., Ron, I. G., Iosilevsky, G., Kennedy, J. A., Revskaya, E., de Kater, A. W., Banaga, E., Klutzaritz, V., Friedmann, N., Galun, E., Denardo, G. L., Denardo, S. J., ... Thornton, G. B. (2013). Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma. Journal of Skin Cancer, 2013, 828329. https://doi.org/10.1155/2013/828329

@article{17cfe8f3c5fd4600804043378650c520,

title = "Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma",

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 (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.",

author = "M Klein and M Lotem and T Peretz and Zwas, {S T} and S Mizrachi and Y Liberman and R Chisin and J Schachter and Ron, {I G} and G Iosilevsky and Kennedy, {J A} and E Revskaya and {de Kater}, {A W} and E Banaga and V Klutzaritz and N Friedmann and E Galun and Denardo, {G L} and Denardo, {S J} and A Casadevall and E Dadachova and Thornton, {G B}",

year = "2013",

doi = "10.1155/2013/828329",

language = "אנגלית",

volume = "2013",

pages = "828329",

journal = "Journal of Skin Cancer",

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Klein, M, Lotem, M, Peretz, T, Zwas, ST, Mizrachi, S, Liberman, Y, Chisin, R, Schachter, J, Ron, IG, Iosilevsky, G, Kennedy, JA, Revskaya, E, de Kater, AW, Banaga, E, Klutzaritz, V, Friedmann, N, Galun, E, Denardo, GL, Denardo, SJ, Casadevall, A, Dadachova, E & Thornton, GB 2013, 'Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma', Journal of Skin Cancer, vol. 2013, pp. 828329. https://doi.org/10.1155/2013/828329

TY - JOUR

T1 - Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma

AU - Klein, M

AU - Lotem, M

AU - Peretz, T

AU - Zwas, S T

AU - Mizrachi, S

AU - Liberman, Y

AU - Chisin, R

AU - Schachter, J

AU - Ron, I G

AU - Iosilevsky, G

AU - Kennedy, J A

AU - Revskaya, E

AU - de Kater, A W

AU - Banaga, E

AU - Klutzaritz, V

AU - Friedmann, N

AU - Galun, E

AU - Denardo, G L

AU - Denardo, S J

AU - Casadevall, A

AU - Dadachova, E

AU - Thornton, G B

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1155/2013/828329

DO - 10.1155/2013/828329

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 23365757

SN - 2090-2905

VL - 2013

SP - 828329

JO - Journal of Skin Cancer

JF - Journal of Skin Cancer

ER -

Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma

Abstract

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