Safety and efficacy of 188-rhenium-labeled antibody to melanin in patients with metastatic melanoma.
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.
Hadassah Medical Center, Hebrew University, Kiryat Hadassah, 91120 Jerusalem, Israel.
M
M
Klein
M
M
Lotem
T
T
Peretz
S T
ST
Zwas
S
S
Mizrachi
Y
Y
Liberman
R
R
Chisin
J
J
Schachter
I G
IG
Ron
G
G
Iosilevsky
J A
JA
Kennedy
E
E
Revskaya
A W
AW
de Kater
E
E
Banaga
V
V
Klutzaritz
N
N
Friedmann
E
E
Galun
G L
GL
Denardo
S J
SJ
Denardo
A
A
Casadevall
E
E
Dadachova
G B
GB
Thornton