REDWOOD CITY, Calif., Sept. 26 ThresholdPharmaceuticals, Inc. (Nasdaq: THLD), today announced that results from aPhase 2 trial of glufosfamide plus gemcitabine were presented at the EuropeanCancer Conference (ECCO) annual meeting in Barcelona, Spain.
In the Phase 2 clinical trial of glufosfamide in combination withgemcitabine for the treatment of advanced pancreatic cancer, six-month andone-year survival were 50% (95% CI: 31-67%) and 32% (95% CI: 16 - 49%),respectively. Median progression-free and overall survival were 3.7 and 6.0months.
"We are encouraged by the results of this Phase 2 study, especially withrespect to the one-year survival data which was higher than expected comparedto previous studies of either gemcitabine alone or in combination withtarceva," said Barry Selick, Ph.D., chief executive officer of Threshold."Based on these findings we believe that glufosfamide should have a role inthe treatment of pancreatic cancer and, taken together with our Phase 3results, we will be exploring the best options for its continued developmentin the treatment of this disease".
In a poster session at ECCO, Dr. Elena (Gabi) Chiorean, Indiana UniversityCancer Center, Indianapolis, IN, presented the Phase 2 results in a posterentitled, "Glufosfamide (GLU) plus gemcitabine (GEM) in pancreaticadenocarcinoma: results of a Phase 2 trial". In the clinical trial, 29patients were treated, of which 28 patients with pancreatic adenocarcinomapreviously untreated with chemotherapy were evaluated for response. Overall, 6of 28 patients (21%; 95% CI: 8-41%) achieved a partial response including oneunconfirmed partial response. Median duration of confirmed responses was 8.4months. In addition, 11 of 28 patients (39%) experienced stable disease(duration 1.2+ to 12.6+ months). Objective response was assessedradiologically after every two cycles (8 weeks) of therapy. A partial responseis characterized as a decrease in size by 30% of the sum of the longestdiameters of target lesions, the absence of progression of all non-targetlesions and no new lesions.
Grade 3 and 4 neutropenia occurred in 8 (28%) and 15 (52%) patients. Grade3 and 4 thrombocytopenia occurred in 8 (28%) and 2 (7%) patients. Fivepatients (18%) had a glufosfamide-related serious adverse event (SAE), whichincluded renal tubular acidosis (RTA) with renal failure (2 patients), RTAalone, vomiting or nausea. Three patients died from an SAE unrelated toglufosfamide. Another patient developed an SAE of renal failure afterhypotension associated with pulmonary embolus. The creatinine clearance (CrCL)fell below 60 mL/min in 10 of 27 (37%) patients with CrCL greater than orequal to 60 at baseline.
These data indicate that glufosfamide plus gemcitabine may benefitpatients with chemotherapy na´ve pancreatic adenocarcinoma. Hematologic andrenal toxicity may be greater than would be expected with either agent alonealthough the small numbers preclude definitive conclusions. No unanticipatedadverse events based on previous experience with glufosfamide were observed.
The Phase 2 poster is available on the Threshold website athttp://investor.thresholdpharm.com/calendar.cfm.
Glufosfamide combines the active part of ifosfamide, a member of a widelyused class of chemotherapy drugs known as "alkylators", with a glucosemolecule. Because of its glucose component and a tumor cell's increased needfor glucose, glufosfamide may be preferentially transported into tumorscompared to most normal tissues. Inside cells, the linkage between glucose andthe alkylator is cleaved to release the active drug.
About Pancreatic Cancer
The American Cancer Society estimates that 37,170 patients will bediagnosed with pancreatic cancer in the United States in 2007, andapproximately 33,370 patients will die from the disease. Only 15-20% of newlydiagnosed patients are