Seattle Genetics, Inc. and Agensys, Inc., an affiliate of Tokyo-based Astellas Pharma Inc., today announced that they have initiated a phase I clinical trial of ASG-5ME for the treatment of metastatic pancreatic cancer. ASG-5ME is an antibody-drug conjugate (ADC) that is being co-developed by both companies for the treatment of solid tumors.
"There is significant need for new pancreatic cancer therapies, demonstrated by the fact that most patients with advanced disease die within one year from diagnosis," said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine at Seattle Genetics. "We believe ASG-5ME, which is an ADC designed to deliver the potent cytotoxic agent MMAE directly to tumor cells, has the potential to provide a new therapeutic option for this aggressive disease."
The single-agent, phase I, open-label, dose-escalation study will evaluate the safety and tolerability of ASG-5ME in patients with pancreatic cancer and identify the maximum tolerated dose. Secondary objectives include assessing the pharmacokinetics and antitumor activity of ASG-5ME and identifying a recommended dose and regimen for future clinical trials. The study is designed to enroll up to approximately 50 patients at multiple centers in the United States.
Dr. David Stover, Vice President and Head of Research at Agensys, noted that ASG-5ME is an ADC composed of a fully human monoclonal antibody directed to SLC44A4 (AGS-5), a novel cancer target identified by Agensys to be upregulated in a number of epithelial tumors.
The antibody is attached to a highly potent, synthetic agent, monomethyl auristatin E (MMAE), via an enzyme-cleavable linker using Seattle Genetics' proprietary technology. The novel linker system is designed to be stable in the bloodstream and release the potent cell-killing agent once inside antigen-expressing cancer cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity. Preclinical data demonstrate that SLC44A4 (AGS-5) is expressed on more than 80 percent of samples derived from patients with pancreatic, prostate and gastric cancers. In addition, ASG-5ME induced long-term regressions in preclinical models of established pancreatic, prostate and colon cancers.