REDWOOD CITY, Calif., July 26 /PRNewswire-FirstCall/ -- Threshold Pharmaceuticals, Inc. , today announced that it has initiated a Phase 1 clinical trial evaluating the safety of TH-302, the Company’s first hypoxia-activated prodrug (HAP), in patients with advanced solid tumors.
“TH-302 is a novel cancer therapeutic specifically activated under the low oxygen or “hypoxic” conditions typical of solid tumor cancer cells,” said Barry Selick, Ph.D., Threshold’s chief executive officer. “Hypoxic tumor cells typically evade traditional anti-cancer drugs that target rapidly dividing cells, ultimately leading to drug resistance, relapse, and metastasis. If TH- 302 can reduce the metastatic potential of tumors or prevent the growth of drug-resistant cancer cells, it could be a significant clinical breakthrough for the treatment of a variety of cancers.” TH-302 is the first compound from Threshold’s Hypoxia-Activated Prodrug (HAP) program to enter human clinical trials, and Threshold is developing other novel HAPs that specifically target tumor hypoxia.
Clinical Trial Design
Approximately 50 patients with advanced solid tumors are planned to enroll in the Phase 1, open-label, dose-escalation clinical trial to be conducted in the United States. Up to six patients per dose level will participate in the dose escalation phase of the trial. Once a maximum tolerated dose (MTD) has been established, six additional patients will be enrolled at the MTD level.
TH-302 is administered as a 30-minute intravenous infusion weekly for three weeks followed by one week off therapy. Patients who have received one or more regimens of chemotherapy, or for whom no effective therapy is available, are eligible for the trial. Patients will not receive any additional chemotherapy while receiving TH-302. Patients who successfully complete a four week treatment cycle without evidence of significant treatment-related toxicity or progressive disease will continue to receive treatment for up to six cycles. Tumor response will be measured at the end of cycles 2, 4 and 6.
The primary objectives of the study are to determine the MTD and dose- limiting toxicities of TH-302 in patients with advanced solid tumors and to establish the appropriate dose for testing in potential Phase 2 clinical trials. The secondary objectives of the trial include establishing the pharmacokinetics and assessing the anti-tumor activity of TH-302, as measured by objective response rate, duration of response, progression-free survival, overall survival, and various safety parameters. Tumors will be evaluated at baseline and every eight weeks using the Response Evaluation Criteria In Solid Tumors (RECIST).
Clinical Rationale
Tumor hypoxia, or regions of very low oxygen concentration in tumor tissues, results from the abnormal and limited blood vessel growth that is a fundamental hallmark of solid tumors. Many solid tumors have significant regions of hypoxia and, because these regions have limited access to the blood supply and oxygen, the cells in them divide slowly, making them resistant to traditional chemotherapy and radiation, which target rapidly dividing cells. Cells in these hypoxic regions are believed to accumulate the genetic mutations that ultimately lead to resistance to the original chemotherapy, relapse, and metastasis. Thus, therapeutics that target hypoxic regions of tumors could provide significant additional anti-tumor activity and clinical benefit over current chemotherapeutic and radiation treatments. Threshold and other companies are pursuing therapies based on this approach.
About TH-302
Threshold’s HAP programs focus on highly active anti-cancer compounds with safety profiles that should be improved by targeting them to the hypoxic regions of solid tumors. TH-302 is a nitroimidazole-linked prodrug of a brominated derivative of an isophosphoramide mustard previously used in cancer drugs such as ifosfamide, cyclophosphamide, and glufosfamide. TH-302 has been shown, in preclinical studies, to be both efficacious and well tolerated. Mark Matteucci, Ph.D., Threshold’s senior vice president of discovery research and leader of its HAP programs said, “TH-302 has shown remarkable activity in animal models of human pancreatic and prostate cancers and is active against a wide variety of other tumor types in both cell-based as well as animal models. We are hopeful that TH-302, alone or in combination with other anti-tumor therapies, will provide a significant improvement in the treatment of cancer patients.” Threshold is actively pursuing additional HAP product candidates, based on already approved as well as novel anti-tumor drugs.
About Solid Tumors
The National Cancer Institute defines a solid tumor as an abnormal mass of tissue. Solid tumors may be benign (not cancerous), or malignant (cancerous). Different types of solid tumors are named for the type of cells that form them. Examples of malignant solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors. The majority of reported cases of cancer and causes of cancer deaths are solid tumors.
About Threshold Pharmaceuticals
Threshold is a biotechnology company focused on the discovery and development of small molecule therapeutics for the treatment of cancer. By selectively targeting abnormally-proliferating tumor cells, the Company’s drug candidates are designed potentially to be more effective and less toxic to healthy tissues than conventional treatments. For additional information, please visit our website (www.thresholdpharm.com).
Forward-Looking Statements
Except for statements of historical fact, the statements in this press release are forward-looking statements, including statements regarding Threshold’s product candidates, clinical trial plans, and potential therapeutic uses and benefits of our product candidates. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Potential risks and uncertainties include, but are not limited to, Threshold’s ability to commence, enroll or complete its anticipated clinical trials, the time and expense required to conduct such clinical trials and analyze data, issues arising in the regulatory or manufacturing process and the results of such clinical trials (including product safety issues and efficacy results). Further information regarding these and other risks is included under the heading “Risk Factors” in Threshold’s Quarterly Report on Form 10-Q, which was filed with the Securities Exchange Commission on May 9, 2007 and is available from the SEC’s website (www.sec.gov) and on our website (www.thresholdpharm.com) under the heading “Investors.” We do not intend to update any forward-looking statement made in this news release.
Contact: Denise T. Powell Sr. Director, Corporate Communications Threshold Pharmaceuticals, Inc. 650-474-8206 dpowell@thresholdpharm.com
Threshold Pharmaceuticals, Inc.
CONTACT: Denise T. Powell, Sr. Director, Corporate Communications ofThreshold Pharmaceuticals, Inc., +1-650-474-8206,dpowell@thresholdpharm.com
Web site: http://www.thresholdpharm.com/
