Threshold Pharmaceuticals (THLD) announced that the target enrollment of 620 patients with advanced soft tissue sarcoma has been achieved in the company’s pivotal phase 3 trial of TH-302, an investigational drug that targets the low-oxygen (hypoxic) characteristic of many solid tumors.. The enrollment achievement triggers a milestone payment of $12.5 million from Merck KGaA. The hope is that by targeting specific cells the drugs will be more effective and less toxic to healthy tissues than non-targeted treatments.
Soft tissue sarcoma (STS) is a cancer occurring in muscle, fat, blood vessels, tendons, fibrous tissues and connective tissue. According to the American Cancer Society, there are approximately 50 types of STS; and in 2013 more than 11,400 new cases will be diagnosed in the U.S., and approximately 4,400 Americans will die from STS. In addition, approximately 40,000 new cases and 13,000 deaths in the U.S. and Europe are part of a growing underserved market.
The trial is enrolling patients with metastatic or locally advanced unresectable soft tissue sarcoma and is designed to evaluate the efficacy and safety of TH-302 in combination with doxorubicin, compared to doxorubicin alone. Target enrollment was increased earlier this year from 450 to 620 to improve the chances of reaching statistical significance in survival following news in March of 2013 that ZIOPHARM Oncology’s (ZIOP) Phase 3 trial for soft tissue sarcoma failed to meet its primary endpoint. The failed trial called into question previous survival assumptions for STS patients on doxorubicin.
Though Threshold will remain blinded to the data from this ongoing Phase 3 trial, an Independent Data Monitoring Committee (IDMC), which monitors patient safety on an ongoing basis, will conduct an interim efficacy and safety analysis after 235 deaths are reported. The interim analysis is projected to be conducted in mid-2014.
We remain skeptical about the long-term potential for hypoxic-targeted tumor therapy. It’s worth noting that TH-302 could potentially compete with CytRx Corporation’s (CYTR) aldoxorubicin for the treatment of soft tissue sarcoma. In December, CYTR announced that its Phase 2b study of aldoxorubicin showed a 80-100% improvement in PFS among patients treated with aldoxorubicin versus doxorubicin.
