The US Food and Drug Administration has reached an agreement with the Germany based Merck KGaA, Threshold Pharmaceuticals' partner for the development and commercialization of TH-302, covering a Special Protocol Assessment (SPA) for a phase III randomized trial of TH-302 in patients with metastatic or locally advanced unresectable pancreatic cancer. The trial is designed to evaluate the efficacy and safety of TH-302 in combination with gemcitabine compared with gemcitabine therapy alone.

Pursuant to Threshold's license and co-development agreement with Merck, Merck will be responsible for conducting the phase III study under the SPA.

A Special Protocol Assessment (SPA) is a written agreement with the FDA that documents FDA's agreement that the design and planned analysis of a study can adequately address objectives in support of a regulatory submission. However, FDA's determinations for marketing application approval are made after a complete review of a marketing application and are based on the entire data in the application.

“In light of the evolving landscape for the first-line treatment of patients with advanced pancreatic cancer, we are pleased with the FDA's agreement that the design and planned analysis of this study adequately address the objectives necessary to support a regulatory submission,” said Barry Selick, PhD, chief executive officer of Threshold. “Given that the phase II clinical trial met its primary endpoint, which was presented earlier this year at the annual AACR and ESMO medical meetings, we and our partner Merck are looking forward to further investigating TH-302 in a phase III study in patients living with this extremely difficult to treat cancer.”

Pancreatic cancer is a malignant neoplasm of the pancreas with current treatment options including surgery, radiotherapy and chemotherapy. Gemcitabine as a single agent or in combination with other treatments is the most commonly used chemotherapeutic agent in patients with advanced pancreatic cancer. The targeted therapy erlotinib, the only other agent approved for treatment of pancreatic cancer since gemcitabine, received regulatory clearance based on results from a phase III study demonstrating a median overall survival of 6.4 months for patients treated with erlotinib in combination with gemcitabine versus 6 months for gemcitabine alone.

TH-302 is a hypoxia-targeted drug designed to be activated under tumour hypoxic conditions, a hallmark of many cancers. Areas of low oxygen levels (hypoxia) are common in many solid tumours due to insufficient blood vessel growth. Similarly, the bone marrow of patients with haematological malignancies has also been shown, in some cases, to be extremely hypoxic.

TH-302 has been investigated in over 700 patients in phase I/II clinical trials to date in a broad spectrum of tumour types, both as a monotherapy and in combination with chemotherapy treatments and other targeted cancer drugs. Threshold has several additional ongoing clinical trials, the most advanced of which is a phase III pivotal study evaluating TH-302 in combination with doxorubicin versus doxorubicin alone in patients with soft tissue sarcoma. Results of the phase II study of TH-302 in patients with pancreatic cancer were reported at the American Association for Cancer Research (AACR) Annual Meeting 2012 and the European Society for Medical Oncology (ESMO) 2012 Congress. In February 2012, Threshold signed a global license and co-development agreement for TH-302 with Merck KGaA, Darmstadt, Germany.

Threshold is a biotechnology company focused on the discovery and development of drugs targeting Tumour Hypoxia, the low oxygen condition found in micro-environments of most solid tumours as well as the bone marrows of some haematologic malignancies.