GlobeImmune Inc. has initiated the phase I clinical trial that was to be conducted at the National Cancer Institute (NCI) to investigate the safety and tolerability of GI-6301, a new Tarmogen product, for patients with metastatic cancers containing brachyury protein. Brachyury is over-expressed in a variety of important tumour types including breast, colon, lung and prostate cancers.

“Targeting the metastatic evolution of cancer is a unique application of our Tarmogen platform and for immunotherapy in general,” said Timothy C Rodell, MD, president and CEO of GlobeImmune. “This trial potentially expands the utility of our Tarmogen platform that has already shown promise in patients with tumours expressing CEA and mutated Ras. We look forward to working with our NCI colleagues to successfully advance GI-6301 through the clinic.”

The GI-6301 Tarmogen was jointly developed by GlobeImmune and NCI under a Collaborative Research and Development Agreement (CRADA).  Preclinical studies supporting the filing of the IND were conducted at the Laboratory of Tumour Immunology and Biology (LTIB) at NCI led by Drs. Claudia Palena and Jeffrey Schlom. The single-centre phase I study will be funded by the NCI. The GI-6301-01 study is an open-label, dose-cohort escalation trial in patients with metastatic cancers with a high incidence of brachyury expression. The primary endpoint of the study is the safety and tolerability of escalating doses of GI-6301 given as a single agent.  Secondary endpoints include levels of brachyury-specific T cells, reduction in brachyury serum markers and circulating tumour cells and evidence of clinical benefit. James L Gulley, MD, PhD, FACP, director of the Clinical Trials Group, LTIB, will be the Principal Investigator for the study.

The GI-6301 Tarmogen consists of whole, heat-killed, recombinant S. cerevisiae yeast genetically modified to express high levels of brachyury protein. Brachyury is over-expressed in cancer cells compared with normal tissue and is believed to play a significant role in the progression of cancer from a localized to metastatic disease (the epithelial-to-mesenchymal transition, or EMT). Targeting brachyury using the GI-6301 Tarmogen is intended to arrest progression of disease by eliminating the subset of tumour cells that acquire drug resistance and the ability to migrate and invade distant tissues.

GlobeImmune is developing a new class of immunotherapy products called Tarmogens that are designed to elicit a targeted T cell immune response to eliminate diseased cells.