Date: 2014-10-17
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 2014 CTOS Annual Meeting in Berlin, Germany
Company: GlobeImmune (USA - CO)
Product: GI-6301 Tarmogen
Action
mechanism: Tarmogen consists of intact, heat-inactivated yeast containing a target protein. Immunization with a Tarmogen results in antigen-specific cellular immune responses against the target protein and reduction in the number of abnormal cells containing the same target antigen. Tarmogens also reduce the number and function of regulatory T cells, thus further enabling the antigen-specific cellular immune response. Tarmogens target the molecular profile that distinguishes a diseased cell from a normal cell but are not required to be custom manufactured for each individual patient. Tarmogens are manufactured by a process that yields a stable, off-the-shelf product candidate that is disease- or antigen-specific. While some antibody may be generated against the yeast, the antibody does not block the activity of the yeast, allowing for repeated administration and boosting of the immune response with additional administrations. Administration of Tarmogens initially results in binding of the yeast to white blood cells called antigen-presenting cells, the most important of which are known as dendritic cells, near the injection site. The dendritic cells are activated as a result of the Tarmogens binding to molecules called Toll-like receptors and other receptor molecules on the surface of the dendritic cell, resulting in the activation of immune signaling molecules called cytokines. The dendritic cell then engulfs the Tarmogen. This results in presentation of peptides, including the antigen from inside the Tarmogen, to cells, known as CD8+ killer T cells, via Class I MHC molecules on the surface of the dendritic cell, resulting in proliferation of identical antigen specific CD8+ T cells. CD4+ helper T cells are so named because one of their roles is to “help” activate killer T cells by expressing a cytokine called interferon gamma, IFNγ. The newly activated CD8+ killer T cells move throughout the body and identify any other cell that expresses the same disease protein as the one recognized by the CD8+ killer T cells. Once the CD8+ killer T cell finds another cell in the body containing the target protein, it can kill the cell using multiple mechanisms.
Disease: late-stage cancers known to express the brachyury protein including chordoma
Therapeutic area: Cancer - Oncology - Rare diseases
Country:
Trial details:
Latest
news: * On October 17, 2014, GlobeImmune announced that updated results from eleven chordoma patients in the GI-6301 Phase 1 trial were presented at the 2014 CTOS Annual Meeting in Berlin, Germany. Christopher R. Heery, M.D., Head, Clinical Trials Group, Laboratory of Tumor Immunology and Biology at the National Cancer Institute (NCI) presented the data during his talk entitled \"NCI Experience Using Yeast-Brachyury Vaccine (GI-6301) in Patients with Advanced Chordoma (Paper 030).\" Results to date from the eleven chordoma patients in this trial include:
The GI-6301 Tarmogen®product candidate targets cancers containing the brachyury protein. The NCI is conducting a Phase 1 safety, immunology and early efficacy trial of GI-6301 monotherapy in patients with late-stage cancers known to express the brachyury protein including chordoma. This presentation updates data GlobeImmune previously reported on seven chordoma patients in the trial.
• GI-6301 has been generally well tolerated, immunogenic, and has shown evidence of clinical activity in both advanced epithelial cancers and chordomas
• Summary results
o One confirmed partial response by RECIST that has continued past one year
o Eight patients with stable disease at day 85 restaging
? Two of these patients had stable disease at study entry
• Study status
o Seven of 11 chordoma patients have left the study due to disease progression
o Four of 11 chordoma patients remain on treatment with stable disease
? Three of these four patients had progressive disease at study entry
• 62% of all patients (all tumor types) evaluated to date in this Phase 1 trial had post-administration brachyury-specific T cell immune responses
• The most common adverse events seen in this trial were mild/moderate injection site reactions.
