Immunovaccine Inc., a clinical stage vaccine company, has agreed to use its lead cancer product, DPX-Survivac, in a study based in Rome designed to extend life for glioblastoma patients.  

The multicenter trial will be led by Professor Marianna Nuti, Ph.D., Department of Experimental Medicine at the University of Rome, and conducted in collaboration with neurosurgeons and oncologists coordinated by Professor Maurizio Salvati, M.D.  Four major trial centres across Italy will be involved, with the cost of the trial being assumed by the university.  The randomized, placebo-controlled study will enroll more than 50 patients with newly diagnosed brain tumours that have been maximally resected.  The study is expected to start in Q4 of 2013.  
 
The phase II study will evaluate DPX-Survivac therapy in combination with temozolomide, the standard of care therapy for newly diagnosed gliobastoma patients following surgery and radiation.  With current standard of care, median overall survival for newly diagnosed glioblastoma patients is less than 24 months with median time to disease recurrence less than seven months.  Temozolomide is used in both the front-line and maintenance setting in treating patients with glioblastoma. It has been reported to have immune-modulating effects making it a suitable drug to combine with cancer vaccines. DPX-Survivac will be applied only during the temozolomide maintenance phase.
 
Patients will be randomized into three groups to receive either DPX-Survivac; a dendritic cell (DC) based survivin vaccine; or, the standard of care with a placebo vaccine. The primary goal of the study is to evaluate the effectiveness of DPX-Survivac. Secondary endpoints will include progression-free survival and overall survival following the proposed combination therapy. Initial data from this trial is expected in the second half of 2014.
 
“We are enthusiastic to apply DPX-Survivac in glioblastoma patients,” stated Dr. Nuti.  “This type of tumour has been demonstrated to express survivin at a high level and DPX-Survivac has demonstrated promising immunogenicity in a clinical trial in ovarian cancer patients. We hope to achieve similar immunogenicity in glioblastoma patients.”
 
Marc Mansour, chief science officer of Immunovaccine, said, “A survivin vaccine has broad utility across different cancer types, and glioblastoma is a good setting for testing the immunologic effects of DPX-Survivac.  This trial allows us to test DPX-Survivac with an interesting immune modulator and in a minimal residual disease setting. This adheres to our principles for applying a therapeutic vaccine in patients with metastatic disease.”
 
Earlier this year, Immunovaccine announced positive results from the company’s phase I clinical trial of DPX-Survivac.  Data showed all patients that had received DPX-Survivac in combination with cyclophosphamide produced targeted immune responses and that there were multiple strong responders among this group who presented circulating target and sustained specific T cells (CD8 T cells) in their blood.  
 
The presence of circulating CD8 T cells is critical in treating cancer because these particular T cells are implicated in identifying cancer cells, infiltrating tumours and killing cancer targets.  Data also demonstrated that the vaccine had no systemic side effects or dose limiting toxicities.  
 
Glioblastoma, the most common form of brain cancer, is a fast-growing tumour type that develops from astrocytes, a type of glial cell present in the brain. The National Cancer Institute estimates that more than 23,000 Americans will be diagnosed with brain and other nervous system tumours in 2013.  Glioblastoma accounts for approximately 15 per cent of all brain tumours.  The current standard of care for glioblastoma patients is maximum surgical resection combined with radiation and concomitant and adjuvant temozolomide therapy.  Median overall survival for newly diagnosed glioblastoma patients is less than 24 months.
 
DPX-Survivac consists of survivin-based peptide antigens formulated in the DepoVax adjuvanting platform. Survivin has been recognized by the National Cancer Institute (NCI) as a promising tumour-associated antigen (TAA) because of its therapeutic potential and its cancer specificity. Survivin is broadly over-expressed in multiple cancer types in addition to ovarian cancer, including breast, colon and lung cancers. Survivin plays an essential role in antagonizing apoptosis, supporting tumour-associated angiogenesis, and promoting resistance to various anti-cancer therapies. Survivin is also a prognostic factor for many cancers and it is found in a higher percentage of tumours than other TAA’s.
 
The DPX-Survivac vaccine is thought to work by eliciting a cytotoxic T-cell immune response against cells presenting survivin peptides on HLA class I molecules. This targeted therapy attempts to use the immune system to search actively and specifically for tumour cells and destroy them. Survivin-specific T-cells have been shown to target and kill survivin-expressing cancer cells while sparing normal cells.
 
DepoVax is a patented formulation that provides controlled and prolonged exposure of antigens plus adjuvant to the immune system, resulting in a strong, specific and sustained immune response with the capability for single-dose effectiveness.  The DepoVax platform possesses impressive flexibility, allowing it to work with a broad range of target antigens in various therapeutic applications.  The technology is also commercially scalable, with potential for years of stability and ease of use in the clinic.
 
Immunovaccine Inc. applies its novel adjuvanting platform to the development of vaccines for cancer therapy, infectious diseases and animal health. The company’s DepoVax platform is a patented formulation that provides controlled and prolonged exposure of antigens plus adjuvant to the immune system.