Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) today announced the initiation of the randomized Phase 2 portion of the trial of IPI-926 in combination with gemcitabine (also known as Gemzar®) in patients with previously untreated, metastatic, pancreatic cancer. The Phase 2 portion of the trial is a double-blind study that will compare treatment with IPI-926 in combination with gemcitabine to treatment with placebo and gemcitabine. The primary endpoint is overall survival. The trial is expected to enroll approximately 120 patients worldwide. Pancreatic cancer, a difficult-to-treat disease with limited therapeutic options, is the fourth leading cause of cancer death in the U.S. and has a five-year survival rate of only six percent.
IPI-926 is a novel, oral molecule that inhibits Smoothened, a key component of the Hedgehog pathway. Inhibition of the Hedgehog pathway represents a fundamentally new approach for addressing a broad range of cancers, including pancreatic cancer. Inhibiting Smoothened with IPI-926 is believed to deplete the dense, fibrous stroma surrounding pancreatic tumors, leading to increased vascularity and facilitating the delivery of chemotherapy to the tumor.
"IPI-926 may represent a novel method for treating pancreatic cancer by altering the tumor microenvironment and improving the delivery of chemotherapy to the tumor," said Charles Fuchs, M.D., MPH, Director, Gastrointestinal Cancer Center at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. "Pancreatic cancer is a very aggressive disease with limited treatment options. The start of this Phase 2 trial marks an important step in exploring the potential of IPI-926 in this area of cancer research."
"Unfortunately, survival has not improved substantially for patients with pancreatic cancer in over 40 years due in large part to the lack of effective treatment options for patients," stated Julie Fleshman, President and CEO of the Pancreatic Cancer Action Network. "The Pancreatic Cancer Action Network encourages all patients to consider clinical trials when exploring treatment options. Clinical trials evaluating potential new treatments for pancreatic cancer, like this study with IPI-926, will hopefully lead to advances with the potential to improve survival for patients."
Trial Design
The Phase 1b/2 clinical trial evaluates the safety and efficacy of IPI-926 in combination with gemcitabine in patients with previously untreated, metastatic pancreatic cancer. The Phase 2 portion of the trial is an international, multi-center, randomized, double-blind, study designed to compare treatment with IPI-926 in combination with gemcitabine to treatment with placebo and gemcitabine in approximately 120 patients. The primary endpoint of the Phase 2 portion of the trial is overall survival. Secondary endpoints include progression free survival, time to progression and overall response rate.
The Phase 1b portion of the study evaluated once-daily oral administration of IPI-926 at escalating doses in combination with weekly intravenous administration of the standard dose of gemcitabine and established 160 mg as the dose of IPI-926 that will be used in the Phase 2 portion of the ongoing trial. Infinity expects to present data from the Phase 1b portion of the trial later this year.
"In less than two years, we have translated a breakthrough preclinical finding of IPI-926 in pancreatic cancer into a randomized, controlled clinical trial, underscoring our commitment to patients fighting this devastating disease," stated Julian Adams, Ph.D., president of research and development at Infinity. "Beyond pancreatic cancer, preclinical data suggest that inhibition of the Hedgehog pathway has application across a broad range of difficult-to-treat cancers, and we are planning to begin additional studies with IPI-926 in 2011."
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