Scott, Andrew M

Tebbutt, Niall C

Lee, Fook-Thean

Cavicchiolo, Tina

Liu, Zhanqi

Gill, Sanjeev

Poon, Aurora M T

Hopkins, Wendie

Smyth, Fiona E

Murone, Carmel

MacGregor, Duncan

Papenfuss, Anthony T

Chappell, Bridget

Saunder, Timothy H

Brechbiel, Martin W

Davis, Ian D

Murphy, Roger

Chong, Geoffrey

Hoffman, Eric W

Old, Lloyd J

2007-06-01

We report a first-in-man trial of a humanized antibody (hu3S193) against the Le(y) antigen.Patients with advanced Le(y)-positive cancers received four infusions of hu3S193 at weekly intervals, with four dose levels (5, 10, 20, and 40 mg/m(2)). The first infusion of hu3S193 was trace labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and immune response were evaluated in all patients.A total of 15 patients (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1 non-small-cell lung cancer) were entered into the study. Transient grade 1 to 2 nausea and vomiting was observed following infusion of hu3S193 at the 40 mg/m(2) dose level only. There was one episode of dose-limiting toxicity with self-limiting Common Toxicity Criteria grade 3 elevated alkaline phosphatase observed in one patient with extensive liver metastases. The biodistribution of (111)In-hu3S193 showed no evidence of any consistent normal tissue uptake, and (111)In-hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases. Hu3S193 displayed a long serum half-life (T(1/2)beta = 189.63 +/- 62.17 h). Clinical responses consisted of 4 patients with stable disease and 11 patients with progressive disease, although one patient experienced a 89% decrease in a lymph node mass, and one patient experienced inflammatory symptoms in cutaneous metastases, suggestive of a biological effect of hu3S193. No immune responses (human anti-human antibody) to hu3S193 were observed.Hu3S193 is well tolerated and selectively targets tumors, and the long half-life and biological function in vivo of this antibody makes it an attractive potential therapy for patients with Le(y)-expressing cancers.

Clinical Cancer Research; 13(11): 3286-92

Clinical Cancer Research

https://ahro.austin.org.au/austinjspui/handle/1/10388

A phase I biodistribution and pharmacokinetic trial of humanized monoclonal antibody Hu3s193 in patients with advanced epithelial cancers that express the Lewis-Y antigen.

Journal Article