The mazda pharma Guide 12th August to 18th August 2013 | Page 63

? ? PHARMACEUTICAL ARTICLE PHASE I TRIAL OF SGN-CD33A IN AML iotechnology company Seattle Genetics, Inc. has initiated phase I clinical trial of SGN-CD33A for patients with acute myeloid leukaemia (AML). SGN-CD33A is a novel antibody-drug conjugate (ADC) utilizing Seattle Genetics' newest ADC technology targeted to CD33, which is expressed on most AML cells. The trial is designed to assess the safety and anti-leukemia activity of SGNCD33A.The CD33 antibody is attached to a highly potent cytotoxic DNA-crosslinking agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb).“AML is a devastating disease with poor prognostic factors and few compelling treatment options, especially in the relapsed disease setting and in patients over the age of 60,” said Jonathan Drachman, MD, senior vice president, Research and Translational Medicine, at Seattle Genetics. “SGN-CD33A is an innovative ADC that utilizes our latest technology, combining a highly potent cellkilling agent with our new engineered antibody (EC-mAb) technology that results in uniform drug-loading. It is designed to be a highly potent ADC directed to the CD33 antigen, which is found on AML cells. We look forward to evaluating its use as a potential treatment option for AML patients.” The study is a phase I, open-label, multicentre, dose-escalation clinical trial. The primary endpoints are the estimation of the maximum tolerated dose and evaluation of the safety of SGN-CD33A. In addition, the trial will evaluate anti-leukaemia activity, pharmacokinetics, progression-free survival and overall survival in patients with CD33-positive AML. The dose escalation portion of the study is designed to evaluate SGN-CD33A administered every three weeks and will enroll up to approximately 90 patients at multiple centres in the United States. Patients who achieve a complete remission are eligible to continue to receive SGN-CD33A at a lower, maintenance dose given every three weeks. Dose escalation cohorts that show evidence of anti-leukemia activity may be expanded to allow for a more comprehensive evaluation of safety and clinical activity. 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