A phase I trial of humanized monoclonal antibody huA33 in patients with early gastric cancer: Imaging studies, biodistribution, pharmacokinetics, immunohistochemistry, and quantitative tumor uptake

Abstract

4142 Background: An open label dose escalation biopsy-based Phase I trial of huA33 in patients with early gastric carcinoma Methods: Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0, 10.0mg/m2.Patients with early gastric carcinoma received infusion of 131I-huA33 one week prior to surgery. Adverse events, imaging studies, biodistribution, tumor biopsies, and immunohistochemical analysis were performed and evaluated. Results: No dose-limiting toxicity was observed during the trial; the maximum tolerated dose was therefore not reached. Although cancer tissues with (+) or (±) by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with (++) or (+++) by frozen and paraffin sections in the biopsied specimen showed positive ex-vivo scan and positive antigen expression in resected gastric cancer specimen, and the biodistribution of the huA33 showed uptake of 131I-huA33. Conclusions: Humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that strongly expresses A33 antigen. These excellent targeting characteristics of the huA33 indicate potential for the targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting. No significant financial relationships to disclose.