FDA Fast Tracks Threshold's TH-302 For Soft Tissue Sarcoma
By Cyndi Root
Threshold Pharmaceuticals reports that the Food and Drug Administration (FDA) has granted Fast Track designation to TH-302 for treatment-naïve patients with metastatic or locally advanced unresectable soft tissue sarcoma (STS). Threshold announced the designation in a press release, stating that, under a Special Protocol Assessment (SPA) with the FDA, the company is conducting an ongoing Phase 3 trial of TH-302. Threshold and Merck KGaA are co-developing and commercializing the novel agent. Barry Selick, Ph.D., CEO of Threshold, said, “The Fast Track designation may provide an added benefit of facilitating the NDA review process. Currently, we anticipate the primary analysis of overall survival of the Phase 3 trial to be conducted in the first quarter of 2016."
TH-302
TH-302 is a hypoxia-activated prodrug. When the drug encounters a low oxygen environment — which is common in many cancers — it activates. The agent releases bromo isophosphoramide mustard (Br-IPM), a DNA alkylating agent that kills tumor cells. Additionally, since the agent targets hypoxic regions, it produces less toxic side effects. Early stage clinical trials of TH-302 are underway for other solid tumors and hematological malignancies. TH-302 was designated an Orphan Drug for the treatment of STS and pancreatic cancer by both the FDA and the European Commission.
TH-302 Trials
Two Phase 3 trials of TH-302 are underway under SPA agreements with the FDA. One trial pairs TH-302 with doxorubicin vs. doxorubicin alone in patients with STS. The other trial (MAESTRO) is evaluating the agent in combination with gemcitabine vs. gemcitabine plus a placebo in patients with advanced pancreatic cancer.
In partnership with the Sarcoma Alliance for Research through Collaboration (SARC), Threshold is testing the efficacy and safety of TH-302 in combination with doxorubicin, compared with doxorubicin alone. Doxorubicin is an anthracycline that works to slow or stop cancer cell growth. It is often used in combination with other medications. The trial’s primary endpoint is overall survival and secondary endpoints include progression-free survival, overall response rate, pharmacokinetics, and safety. Threshold is conducting the trial of 640 patients at 81 sites worldwide.
About Threshold Pharmaceuticals
Threshold Pharmaceuticals is headquartered in San Francisco where it focuses on drugs that take advantage of tumor hypoxia. To help identify patients who might respond to hypoxia-targeted therapeutics, Threshold acquired a Positron Emission Tomography imaging agent from Siemens. The agreement between Threshold and Merck is a global license and co-development agreement for TH-302 with an option for Threshold to co-commercialize TH-302 in the U.S. following regulatory approval.