CAMBRIDGE, Mass., March 30, 2009 (GLOBE NEWSWIRE) -- Infinity Pharmaceuticals, Inc. (Nasdaq:INFI), an innovative cancer drug discovery and development company, today announced the initiation of a Phase 2 clinical trial of IPI-504 (retaspimycin hydrochloride), its lead heat shock protein 90 (Hsp90) inhibitor, in combination with Herceptin(r) (trastuzumab) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. IPI-504 has demonstrated the potential to disrupt the activity of multiple proteins and cell signaling pathways implicated in tumor growth, including HER2, a key signaling pathway in breast cancer.
"This trial will explore the combination of two targeted agents, IPI-504 and trastuzumab (Herceptin), which should complement each other by disrupting HER2 signaling in different ways," said Clifford A. Hudis, M.D., Chief of the Breast Cancer Medicine Service and Attending Physician at Memorial Sloan-Kettering Cancer Center and an investigator in the trial. "In earlier trials with a related agent we documented clear evidence of activity when Hsp90 inhibition is added to trastuzumab in patients with HER2-positive breast cancer. I look forward to further exploring IPI-504's potential activity in this exciting area."
The goal of this open-label, international, multi-center Phase 2 clinical trial is to evaluate the safety and anti-tumor activity of IPI-504 in combination with Herceptin in patients with pretreated, locally advanced or metastatic HER2-positive breast cancer. IPI-504 is being administered intravenously at 300 mg/m2 on a three-week cycle, consisting of twice-weekly treatment for two weeks followed by one week off treatment. Herceptin will be administered intravenously once every three weeks. Evidence of anti-tumor activity will be evaluated using RECIST criteria (Response Evaluation Criteria in Solid Tumors). The Phase 2 study will enroll a total of 46 patients and Infinity anticipates presenting preliminary data in mid-2010.
"By blocking HER2 signaling through a novel mechanism, IPI-504 may provide a new option for patients with HER2-positive breast cancer -- one that may overcome resistance to HER2 targeted agents," said Jose Baselga, M.D., chairman of the Medical Oncology Service and director of the Division of Medical Oncology, Hematology, and Radiation Oncology at the Vall d'Hebron University Hospital in Barcelona, Spain, professor of Medicine at the Universidad Autonoma de Barcelona and an investigator in the trial.
Preclinical data suggest that the HER2 oncoprotein is degraded rapidly when Hsp90 is inhibited by IPI-504, which eliminates HER2 signaling and ultimately causes the tumor cell to die. Infinity researchers have demonstrated that IPI-504 potently inhibits the growth of tumor cells when administered as a single agent in both Herceptin-sensitive as well as Herceptin-resistant breast cancer xenograft models. Moreover, in these models, the combination of IPI-504 and Herceptin results in more robust anti-tumor activity than when either agent was administered alone.
"We believe the demonstrated potency and tumor growth inhibition we've seen in preclinical models of HER2-positive breast cancer with IPI-504 and the sensitivity of the HER2 protein to Hsp90 inhibition could position anti-chaperone therapy as a key component in the treatment of HER2-positive breast cancer," said David S. Grayzel, M.D., vice president, clinical development and medical affairs at Infinity.
Infinity is evaluating the potential of Hsp90 inhibition in a broad range of cancers, The RING trial is an international Phase 3 registration trial in patients with refractory gastrointestinal stromal tumors that positions IPI-504 as the potential first-in-class Hsp90 inhibitor. IPI-504 is also being evaluated in a Phase 2 study in patients with advanced non-small cell lung cancer and in a Phase 1b combination study with Taxotere(r) (docetaxel) in patients with advanced solid tumors. Infinity anticipates presenting data from both of these studies in mid-2009. Infinity is also evaluating its oral hsp90 inhibitor, IPI-493, in a Phase 1 study in patients with advanced solid tumors, and anticipates reporting preliminary data from this study by the end of 2009.
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 a number of 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 anti-chaperone agents, IPI-504 (i.v.) and IPI-493 (oral), which have shown potent and selective inhibition of Hsp90 in preclinical studies.
About HER2-Positive Breast Cancer
The American Cancer Society (ACS) reports that among American women, breast cancer is the most common form of cancer. The ACS estimates that approximately 182,000 new cases of breast cancer were diagnosed in women in the United States in 2008. Statistically, one in eight women will be diagnosed with invasive breast cancer in her lifetime. Studies show that approximately 25 percent of breast cancer patients have an over-expression of a protein called Human Epidermal Growth Factor Receptor 2, or HER2, and this over-expression is referred to as HER2-positive. HER2 is a protein that stimulates cancer cells to divide and protects them from cell death. HER2-positive breast cancer is an aggressive subtype of breast cancer. While current therapies targeting HER2 have demonstrated significant clinical benefit, a substantial number of patients with HER2-positive breast cancer develop recurrent disease, for which novel therapies are needed.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative cancer drug discovery and development company 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. Infinity's two most advanced programs in Hsp90 inhibition and Hedgehog signaling pathway inhibition 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 utility of IPI-504 in HER2-positive breast cancer; future clinical trial activity of IPI-504; the potential of IPI-504 to be the first-to-market Hsp90 inhibitor, and the presentation of additional clinical data on 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 IPI-504 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 for IPI-504 and competitor Hsp90 inhibitors, 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; decisions made by organizations evaluating data for presentation or publication; Infinity's ability to obtain additional funding required to conduct its research, development and commercialization activities; unplanned cash requirements and expenditures; Infinity's ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; and Infinity's reliance on its strategic alliance partners for financial support. These and other risks which may impact management's expectations are described in greater detail under the caption "Risk Factors" included in Infinity's annual report on Form 10-K filed with the Securities and Exchange Commission on March 13, 2009. 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.
Herceptin(r) and Taxotere(r) are registered trademarks of Genentech, Inc. and sanofi-aventis llc, respectively.