CAMBRIDGE, Mass., Oct. 24, 2008 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI) today announced initiation of a Phase 3 registration trial of IPI-504 (retaspimycin hydrochloride), its lead inhibitor of heat shock protein 90 (Hsp90), in patients with refractory gastrointestinal stromal tumors (GIST). Initiation of the Phase 3 trial of IPI-504 follows promising safety and activity data reported earlier this year from a Phase 1 study in patients with refractory GIST and other soft tissue sarcomas. The trial is expected to be completed within approximately two years, positioning IPI-504 as the potential first-in-class Hsp90 inhibitor.
The RING (Retaspimycin hydrochloride IN GIST) trial is a randomized, double-blind, placebo-controlled study evaluating approximately 200 patients with refractory GIST in over 20 countries and 50 sites worldwide. Patients whose tumors have grown despite treatment with at least imatinib and sunitinib are eligible to enroll in the RING trial and there is no limit to the number of prior therapies they may have received. The primary endpoint of the study is progression free survival (PFS); secondary endpoints include disease control rate, time to progression, and overall survival. Patients will be randomized 2:1 to IPI-504 or placebo, with a cross-over to treatment with IPI-504 if progression occurs. Response is being evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Imaging with CT scans will be obtained at early time points to enable close monitoring of tumor activity.
"Patients and physicians battling GIST are in need of new therapies with a novel mode of action to address the increasingly prevalent problem of resistance to conventional tyrosine kinase inhibitors," said George D. Demetri, M.D., director of the Ludwig Center at the Dana-Farber/Harvard Cancer Center and principal investigator of the trial. "Targeting Hsp90 represents a highly innovative approach to address the life-threatening problems faced by patients living with GIST whose tumors have become resistant to other therapies. Through the RING study, our worldwide community of investigators and GIST experts is committed to testing the utility of the Hsp90 inhibitor IPI-504 in this disease."
"The start of the RING trial signals an important advance in the global development of our lead anti-cancer agent and extends Infinity's commitment to discover, develop, and deliver to patients new medicines for the treatment of cancer," said Steven H. Holtzman, president, chair, and chief executive officer of Infinity. "The RING trial is anticipated to be completed in approximately two years, potentially enabling IPI-504 to be the first medicine inhibiting the Hsp90 chaperone to market. We believe that anti-chaperone therapy will become an important component in the treatment paradigm for multiple forms of cancer."
For more information about the RING trial, please visit www.RINGtrial.com or call 1-877-504-INFI (4634) to speak to a member of the RING trial support team.
The RING trial is being conducted by Infinity in collaboration with AstraZeneca.
Phase 1 Results of IPI-504 in GIST
Positive results from a Phase 1 study evaluating IPI-504 in patients with metastatic and/or unresectable GIST and other soft tissue sarcomas were presented during the annual meeting of the American Society for Clinical Oncology (ASCO) in June 2008. Results showed that patients with GIST (n=36), who were heavily pre-treated, experienced a 70 percent overall disease control rate, with 3 percent Partial Response and 67 percent Stable Disease at six weeks. Estimated median progression free survival for these patients was 12 weeks.
Targeting Heat Shock Protein 90 (Hsp90) and the Chaperone System
Hsp90 is a central component of the cellular chaperone system -- a system that supports and stabilizes cancer-causing proteins such as c-Kit, EGFR, and HER2, enabling multiple forms of cancer to thrive. Inhibition of the Hsp90 chaperone knocks out this critical source of support for cancer cells, leading to tumor growth inhibition and cancer cell death. Anti-chaperone therapy via inhibition of Hsp90 may represent a significant yet currently unaddressed strategy for treating patients with cancer. Infinity is developing two proprietary agents, IPI-504 (i.v.) and oral IPI-493, which have shown potent and selective inhibition of Hsp90 in preclinical studies.
IPI-504 is being evaluated in the RING (Retaspimycin hydrochloride IN GIST) trial, an international Phase 3 registration study of IPI-504 in patients with refractory gastrointestinal stromal tumors. IPI-504 is also being evaluated in the Phase 2 portion of a Phase 1/2 trial in patients with advanced non-small cell lung cancer and a Phase 1b trial in combination with docetaxel in patients with solid tumors. Additional clinical studies of IPI-504 are anticipated to begin by early 2009. Infinity and AstraZeneca have also initiated a Phase 1 study of IPI-493 in patients with advanced solid tumors.
About Gastrointestinal Stromal Tumors (GIST) and Hsp90
The American Cancer Society (ACS) reports that GIST is the most common form of gastrointestinal sarcoma, a life-threatening disease highly resistant to traditional cytotoxic chemotherapy and radiation treatment. According to the ACS, 4,500 - 6,000 people develop GIST annually in the United States. In Europe, 5,000 - 10,000 people develop GIST annually according to a 2005 report in "Cancer" by Nilsson, et. al. The ACS reports that approximately 100,000 individuals are living with the disease. In the majority of GIST cases, specific mutations in cellular signaling enzymes (kinases) called KIT or PDGFRA cause the growth and survival signal of the cell to become permanently active, leading to cancer. Both KIT and PDGFRA are stabilized by Hsp90, suggesting that inhibition of Hsp90 in GIST is an attractive area for clinical study.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative cancer drug discovery and development company that is seeking to discover, develop, and deliver to patients best-in-class medicines for the treatment of cancer and related conditions. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging cancer pathways with the goal of bringing better drugs to patients. Infinity's two most advanced programs targeting heat shock protein 90 and the Hedgehog signaling pathway are evidence of its innovative approach to oncology drug discovery and development. For more information on Infinity, please refer to the company's website at http://www.infi.com.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding the potential utility of IPI-504, IPI-493, and other drugs targeting the Hsp90 chaperone to treat cancer; the timetable for completion of the RING trial; the ability of IPI-504 to be a first-in-class Hsp90 inhibitor; and future clinical trial activity for IPI-504. Such statements are subject to numerous factors, risks, and uncertainties that may cause actual events or results to differ materially from the company's current expectations. For example, there can be no guarantee that any product candidate Infinity is developing will successfully complete necessary preclinical and clinical development phases. In particular, management's expectations could be affected by risks and uncertainties relating to: results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites, and publication review bodies; Infinity's ability to enroll patients in its clinical trials; Infinity's dependence on its collaboration with AstraZeneca; the results and timing of clinical trials conducted by third parties on other Hsp90 inhibitors; Infinity's ability to obtain additional funding required to conduct its research, development, and commercialization activities; unplanned cash requirements and expenditures; and Infinity's ability to obtain, maintain, and enforce patent and other intellectual property protection for any product candidates it is developing. These and other risks that may impact management's expectations are described in greater detail under the caption "Risk Factors" included in Infinity's quarterly report on Form 10-Q for the quarter ended June 30, 2008, as filed with the Securities and Exchange Commission on August 6, 2008. Further, any forward-looking statements contained in this press release speak only as of the date hereof, and Infinity expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise.