Interim results from Seattle Genetics’ ASG-5ME phase I trial on metastatic PDA

Seattle Genetics, Inc. (Nasdaq: SGEN) today presented interim results from a phase I clinical trial evaluating ASG-5ME for the treatment of metastatic pancreatic ductal adenocarcinoma (PDA) at the American Society of Clinical Oncology (ASCO) 2013 Gastrointestinal Cancers Symposium being held January 24-26, 2013 in San Francisco, CA. ASG-5ME is an antibody-drug conjugate (ADC) targeting the SLC44A4 antigen and is being co-developed by Seattle Genetics and Agensys, Inc., an affiliate of Tokyo-based Astellas Pharma Inc., for the treatment of solid tumors. The phase I data from the ASG-5ME clinical trial in advanced pancreatic cancer identified the maximum tolerated dose (MTD) for weekly administration, demonstrated tolerability and provided preliminary evidence for antitumor activity.

"Pancreatic cancer is a terrible disease, with a median survival of only six months for metastatic disease and a five-year survival rate of less than six percent," said Jonathan Drachman, M.D., Senior Vice President, Research and Translational Medicine of Seattle Genetics. "There is an urgent need to identify more effective therapeutic options for these patients, and we are encouraged by the tolerability and evidence of antitumor activity observed in this phase I trial. We look forward to further results from ongoing trials of ASG-5ME in prostate and gastric cancer."

ADCs are monoclonal antibodies that are designed to deliver cytotoxic agents selectively to tumor cells. This approach is designed to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. With over a decade of experience and knowledge in ADC innovation, Seattle Genetics has developed proprietary technology employing synthetic cytotoxic agents, such as monomethyl auristatin E (MMAE), and stable linker systems that attach these cytotoxic agents to the antibody. Seattle Genetics' linker systems are designed to be stable in the bloodstream and release the cell-killing agent once inside targeted cancer cells. ADCETRIS^® (brentuximab vedotin) is the first drug approved utilizing Seattle Genetics' ADC technology.

A Phase I Study of ASG-5ME, a Novel Antibody-Drug Conjugate, in Pancreatic Ductal Adenocarcinoma (Abstract #176)

A phase I clinical trial was conducted to evaluate the safety and activity and to identify the MTD of ASG-5ME in patients with metastatic PDA. At the time of data analysis, 35 patients with metastatic PDA were enrolled in the trial. These patients had a median age of 63 and were heavily pretreated with a median of three prior therapies. The median time since initial PDA diagnosis and time since identification of metastatic disease was 1.4 years and 0.59 years, respectively. Patients received doses ranging from 0.3 milligrams per kilogram (mg/kg) to 1.5 mg/kg administered weekly for three out of every four weeks.

Key findings included:

• The MTD was identified as 1.2 mg/kg weekly. Of the 35 patients who participated in the trial at the time of analysis, 18 were treated at the MTD.
• Best response for the 18 patients treated at 1.2 mg/kg weekly included one patient (six percent) who achieved a partial response, six patients (33 percent) with stable disease and four patients (22 percent) who had progressive disease. Seven patients (39 percent) were not evaluable for response.
• The most common adverse events occurring in patients at the MTD included fatigue (50.0 percent), vomiting (44.4 percent), decreased appetite (38.9 percent), abdominal pain (33.3 percent) and nausea (33.3 percent).
• The most common Grade 3 or 4 adverse events occurring in patients at the MTD included fatigue (27.8 percent), abdominal pain (22.2 percent), vomiting (16.7 percent) and neutropenia (16.7 percent).

Enrollment of PDA patients to this ASG-5ME phase I trial is complete. Enrollment of patients with relapsed or refractory gastric adenocarcinoma is ongoing. In addition, Seattle Genetics and Agensys are evaluating ASG-5ME in a phase I study for castration-resistant prostate cancer (CRPC).