Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors.
OBJECTIVE
The antibody J591 targets the external domain of prostate-specific membrane antigen, which is expressed in the neovasculature of nonprostate solid tumors. This phase I trial tested the hypothesis that J591 could be used as a vascular targeting platform for patients with nonprostate solid tumors.


METHODS
Patients with progressive solid tumors were eligible. Twenty patients, divided into six dosage cohorts of 3 to 6 patients each, were treated every 3 weeks to a maximum of four doses using either 5, 10, 20, 40, 60, or 100 mg of J591 antibody. Two milligrams of antibody were labeled with 10 mCi of indium-111.


RESULTS
Patients with a wide variety of solid tumors were tested; all had good tumor localization. No dose-limiting toxicities were observed. The serum clearance rate decreased with increasing antibody mass, likely a result of early hepatic uptake of antibody. Half-life for each successive cohort was 0.71, 0.84, 1.86, 1.83, 3.32, and 3.56 days. Hepatic saturation seemed to occur by 60 mg. Seventeen of 18 (94%) patients with soft tissue disease on standard scans showed uptake in the soft tissues on antibody scans as did 6 of 6 patients with bone disease.


CONCLUSIONS
The tumoral neovasculature of a variety of solid tumors can be selectively and safely targeted using J591. In planning for future studies using J591 as a radiation delivery platform, an antibody mass of 60 mg should be considered, as it would seem to minimize the radiation delivered to the liver while minimizing the radiation dose to bone.
Morris
Michael J
MJ
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. morrism@mskcc.org
Pandit-Taskar
Neeta
N
Divgi
Chaitanya R
CR
Bender
Samantha
S
O'Donoghue
Joseph A
JA
Nacca
Angelo
A
Smith-Jones
Peter
P
Schwartz
Lawrence
L
Slovin
Susan
S
Finn
Ronald
R
Larson
Steven
S
Scher
Howard I
HI
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
D000911:Antibodies, Monoclonal; C478680:J591 monoclonal antibody