Threshold Pharm : IDMC Recommends To Continue Late-stage TH-302 Trial

(RTTNews) - Threshold Pharmaceuticals Inc. (THLD) announced Monday that the Independent Data Monitoring Committee or IDMC has completed the planned interim efficacy and safety analyses of unblinded data for the Company's pivotal Phase 3 clinical trial of TH-302 in combination with doxorubicin versus doxorubicin alone in patients with locally advanced unresectable or metastatic soft tissue sarcoma or STS. Based on their analyses, which included an assessment of both benefit and risk, the IDMC recommended that the trial should continue as planned to its natural conclusion.

Threshold and its partner Merck KGaA, Darmstadt, Germany, have been and will remain blinded to the data from the trial. Based on projections derived from the interim analysis, Threshold said it is revising its guidance on timing for the number of events (deaths) required for the primary efficacy analysis.

Previously, the Company projected the pre-specified number of events (n=434) would occur around the middle of 2015; the revised projections suggest the requisite events will occur in the latter half of 2015.

Threshold noted that it is conducting this international, randomized pivotal Phase 3 clinical trial in partnership with the Sarcoma Alliance for Research through Collaboration (SARC) and under a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA). The trial is designed to investigate the efficacy and safety of TH-302 in combination with doxorubicin, compared with doxorubicin alone, in previously untreated patients with metastatic or locally advanced unresectable STS.

The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, overall response rate, pharmacokinetics and safety. Patients were randomized to either doxorubicin alone or to receive TH-302 300 mg/m2 administered intravenously on Days 1 and 8 with doxorubicin 75 mg/m2 on Day 1 of each 21-day cycle.

After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302 according to the same dosing schedule, 300 mg/m2 Days 1 and 8 of each 21-day cycle. The trial enrolled a total of 640 patients across 81 study sites in Europe, Israel, North America and the Russian Federation.

A total of 256 deaths were included in the interim analysis; the statistical hurdle for demonstrating efficacy required a one-sided p-value of < 0.0035 with associated hazard ratio of about < 0.71. The primary analysis, which will now be conducted after a minimum of 434 deaths, will require a one-sided p-value of < 0.0239 with associated hazard ratio of about < 0.82 to reach statistical significance.