A phase I trial of the single-chain immunotoxin SGN-10 (BR96 sFv-PE40) in patients with advanced solid tumors

James A. Posey, Mohammad B. Khazaeli, Michael A. Bookman, Anahit Nowrouzi, William E. Grizzle, Jennifer Thornton, Delicia E. Carey, Jennifer M. Lorenz, Amy P. Sing, Clay B. Siegall, Albert F. LoBuglio, Mansoor N. Saleh

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109 Citations (Scopus)


Purpose: Our purpose in the study was to establish the maximum tolerated dose and toxicity profile of SGN-10 (or BR96 sFv-PE40), a single-chain immunotoxin. SGN-10 is composed of the fused gene products encoding the translocating and ADP-ribosylating domains of Pseudomonas exotoxin (PE40) and the variable heavy (VH) and variable light (VL) regions of BR96 monoclonal antibody. This antibody is specific for a LewisY (LeY)-related carbohydrate antigen expressed on multiple carcinomas. Experimental Design: A total of 46 patients with LeY-positive metastatic carcinoma were enrolled in a Phase I dose-escalation study in cohorts of three to six patients who received SGN-10 at doses ranging from 0.024 to 0.962 mg/m2, administered on days 1, 4, 8, and 11, followed by 2 weeks of rest and a second cycle of therapy. Pharmacokinetics and human antibody response to SGN-10 were also determined. Results: The maximum tolerated dose of SGN-10 was 0.641 mg/m2 with gastrointestinal dose-limiting toxicity. Pharmacokinetic studies performed in eight patients at the 0.641-mg/m2 dose revealed a t[1/2] of 2.5 ± 0.3 h and a Cmax of 389 ± 112 ng/ml. Pharmacodynamic analyses demonstrated a rapid clearance of the drug by day 11 associated with an antitoxin human antitoxin antibody (HATA) response in most patients. Signs consistent with a modest vascular leak syndrome, specifically, transient hypoalbuminemia, were observed in patients treated with doses of ≥0.384 mg/m2. No complete or partial tumor responses were observed at an 8-week evaluation, although 31% of patients had stable disease. Conclusions: The maximal tolerated dose of SGN-10 given twice weekly for 2 weeks is 0.641 mg/m2 with gastrointestinal dose-limiting toxicity. The immunogenicity of the toxin moiety limits the ability of SGN-10 to circulate by day 11 of therapy. Studies are ongoing to evaluate strategies to ameliorate toxicities and to inhibit the development of the anti-SGN-10 immune response.

Original languageEnglish
Pages (from-to)3092-3099
Number of pages8
JournalClinical Cancer Research
Issue number10
Publication statusPublished - 1 Oct 2002
Externally publishedYes


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