Threshold Pharmaceuticals, Inc. announced clinical trial results related to Threshold's clinical stage hypoxia-activated pro-drug, TH-302. The results were presented at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics taking place in Berlin, Germany in November.

Today's presentation focused on two clinical trials, the 402 trial and the 403 trial. The 402 trial is a Phase 1/2, three arm, multi-centre, dose escalation and dose expansion trial to determine the safety, efficacy and pharmacokinetics of TH-302 in combination with gemcitabine (Gem) or docetaxel (Doc) or pemetrexed (Pem) in patients with various advanced solid tumours including, but not limited to, advanced or metastatic pancreatic cancer, Castrate-Resistant Prostate Cancer (CRPC) and relapsed or refractory Non-Small Cell Lung Cancer (NSCLC). The 403 trial is investigating TH-302 in combination with doxorubicin (Dox) in patients with advanced soft tissue sarcoma. Presentation primarily discussed the results for those patients with pancreatic cancer, CRPC, recurrent NSCLC, and soft tissue sarcoma.

Additionally, in the gemcitabine treatment arm, median Progression Free Survival (PFS) was 6.4 months (95% CI: 4.7 to 7.7 months). Among the patients with relapsed or refractory NSCLC, median PFS was 4.2 months (95% CI: 2.8 months to not reached). Among the 15 patients with CRPC, 11 (73%) had a PSA decline of at least 50%. Among the patients with soft tissue sarcoma, median PFS was 6.4 months (95% CI: 5.6 to 6.9 months). Overall, hematologic toxicity was acceptable and skin and mucosal toxicities were well managed at current dose levels.

“We designed TH-302 to specifically address a significant unmet need in the treatment of cancer and, in so doing, complement those other approaches that comprise the mainstay of cancer therapy. These results suggest that TH-302 is behaving as designed with broad activity against multiple tumour types and in all combinations with which it has been evaluated. TH-302 is well-tolerated and the activity seen in all combinations is greater than what would be expected from any of the individual chemotherapy agents alone,” said Charles Hart, PhD, Threshold's vice president of biology. “A definitive randomized comparison of the combination versus the chemotherapy alone has been initiated in pancreatic cancer with results expected in 2011 and we look forward to continuing our investigations in additional indications.”

Threshold is a biotechnology company focused on the discovery and development of drugs targeting Tumour Hypoxia, the low oxygen condition found in microenvironments of most solid tumours. This approach offers broad potential to treat most solid tumours. By selectively targeting tumour cells, we are building a pipeline of drugs that hold promise to be more effective and less toxic to healthy tissues than conventional anticancer drugs.