Immunovaccine, a clinical stage vaccine company, presented positive data from clinical and preclinical vaccine studies, including DPX-Survivac, the company’s lead therapeutic cancer vaccine, recently at the annual meeting of American Association for Cancer Research (AACR) 2014.
In a poster presentation, Immunovaccine highlighted results demonstrating that metronomic cyclophosphamide (mCPA), an immune modulating agent, enhanced the immunogenicity of DepoVax-based vaccines in preclinical cancer models consistent with previously reported Phase I data showing a similar enhancement of DPX-Survivac in patients. Importantly, the animal studies demonstrated the combination therapy’s ability to eliminate advanced tumours that could not be treated with vaccine or mCPA alone.
Tumours exposed to the combination therapy specifically exhibited an increase in T cell activation markers, suggesting increased immune-mediated anti-tumour activity at the tumour site with the vaccine/mCPA therapy and further supporting the use of the combination therapy in clinical trials.
The addition of anti-PD-1 checkpoint inhibitor to the DepoVax vaccine/mCPA combination resulted in further enhanced anti-tumour activity, which allowed the treatment of more advanced tumours. The effective tumour regressions that were observed could not be achieved without the use of vaccine or the use of anti-PD-1.
Checkpoint proteins are known to suppress immune activity and their expression was increased in tumours under immune attack from the vaccine therapy. Down-regulating suppressive mechanisms at the tumour level with the use of checkpoint inhibitors allowed the robust vaccine therapy to cause tumour regressions in animals, suggesting that the triple combination of vaccine, cyclophosphamide and anti-PD-1 may be well suited for the treatment of patients with aggressive tumours who may not otherwise respond to a less aggressive vaccine therapy.
“These study results represent strong support for Immunovaccine’s belief that combination immunotherapies will be essential to treat cancer,” said Marc Mansour, chief operating officer of Immunovaccine. “Combining a vaccine with immune modulators like cyclophosphamide may be most effective in patients with no evidence of disease and with a high rate of recurrence, while combining vaccine-based therapies with synergistic checkpoint inhibitors may be particularly useful for patients with more aggressive disease.”
A second poster presentation related to DPX-Survivac will also be made during the AACR conference by an Immunovaccine collaborator, Caprion’s ImmuneCarta business unit. This presentation, which will take place on Wednesday, April 9, will detail immune response results from Immunovaccine’s Phase I study of DPX-Survivac in ovarian cancer patients. Findings demonstrated that treatment with DPX-Survivac induced durable target T cell responses, with these responses more robust when DPX-Survivac was combined with cyclophosphamide as an immune modulator. These results are consistent with the preclinical study results presented at AACR and provide further support for the potential for combining DPX-Survivac with complementary immune modulators and immunotherapies.
Immunovaccine expects a large randomised Phase II trial of DPX-Survivac to be initiated in 2014 in ovarian cancer. The 250 patient trial will be sponsored and conducted by Canada’s NCIC Clinical Trials Group (NCIC CTG). Additionally, researchers at the University of Rome will be initiating a Phase l/II trial of DPX-Survivac in glioblastoma (brain cancer) with the first patient receiving the vaccine in the first half of 2014.