November 19, 2009 (FinancialWire) — Threshold Pharmaceuticals, Inc. (NASDAQ: THLD) announced clinical trial results related to Threshold’s clinical stage hypoxia-activated prodrug, TH-302. The results were presented yesterday at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics being held November 15 to 19, 2009, in Boston, MA.
“Prostate cancer is known to be hypoxic. Several years ago we furthered the support for the rationale of using TH-302 to treat prostate cancer when TH-302 was combined with docetaxel in a preclinical metastatic model of prostate cancer and eradicated all signs of disease,” said Charles P. Hart, Ph.D., Threshold’s vice president of Biology. “This week we have summarized both the benchwork data and initial clinical data. We are excited to continue investigations with TH-302 and with the potential benefit that it might confer to people living with prostate cancer.”
The presentation summarized a series of translational models and select results from two clinical trials of TH-302. Results from these clinical trials were previously discussed at various medical meetings this year. The two clinical trials are both evaluating the safety and preliminary efficacy of TH-302 in patients with advanced solid tumors; one in combination with other chemotherapy agents (the 402 trial) and the other with TH-302 as monotherapy (the 401 trial). In this presentation, results from patients with metastatic castration-resistant prostate cancer were discussed. Results from 14 patients with metastatic CRPC from the two clinical trials were presented in a poster entitled “Bench to Bedside Experience with TH-302: a Tumor-Selective Hypoxia-Activated Prodrug as a Promising Treatment for Prostate Cancer.”
In the 401 trial, 8 patients with metastatic CRPC enrolled in the trial and received TH-302 as monotherapy. All 8 patients had bone metastases and 5 of the 8 patients also had lymph node metastases. TH-302 was administered on days 1, 8 and 15 of a four week cycle. The median dose of TH-302 administered to the 8 patients enrolled in the dose escalation component of the trial was 480 mg/m2 (30 to 670 mg/m2). The patients received a median of 3 cycles of TH-302 (range: 1 to 6 cycles). Tumors were assessed using RECIST (Response Evaluation Criteria In Solid Tumors). Six of 7 evaluable patients had stable disease at their initial tumor assessment after Week 8. In the 401 clinical trial mucosal and skin toxicity were dose-limiting while hematologic toxicity was minimal.
In the 402 trial, docetaxel is one of three chemotherapeutic regimens being evaluated in combination with TH-302 which is given on days 1 and 8 of a three week docetaxel cycle. Docetaxel is administered at the full prescribed dose of 75 mg/m2. The maximum tolerated dose of TH-302 in combination with docetaxel was established at 340 mg/m2. Data from the first 6 patients with metastatic CRPC enrolled in the trial were presented. Patients received a median of more than 5 cycles of TH-302 (range: 1 to 8+ cycles). Three patients continue on the trial and have received a median of 6 cycles of treatment. Four patients had at least one evaluable post-treatment tumor assessment. Three of 4 patients had SD or better including one patient with a confirmed partial response. One of 4 patients discontinued with progressive disease with the onset of bone metastases. Four patients had prostate specific antigen assessments after at least 2 cycles of therapy with drop in median PSA of 62 percent. Three of 4 patients had a drop in PSA of at least 50 percent. Skin and mucosal toxicities were not dose limiting. Grade 1 mucosal toxicity was reported in 3 of 6 patients. Skin toxicity of grade 1 or 2 was reported in 4 of 6 patients. Grade 3 neutropenia was reported in 2 patients, one continues on study after a dose reduction and the other continues on study at the full dose of TH-302. Enrollment of patients with metastatic CRPC continues in the 402 trial with the objective of better defining the possible therapeutic benefit of TH-302 combined with docetaxel in this setting.
The company has an additional ongoing clinical trial (the 403 trial) of TH-302. The 403 trial is a Phase 1/2 clinical trial of TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.
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