In a poster presentation at the conference, Immunovaccine highlighted promising early evidence of clinical activity for DPX-Survivac in ovarian cancer patients. One patient, who experienced a 43% reduction in tumor size, was classified as a partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). The PR, which persisted following discontinuation of treatment, was accompanied by reduction in levels of a commonly used ovarian cancer biomarker (CA125) and a significant increase in vaccine-induced immune responses. The patient’s tumor and CA125 levels remain stable eight months following initiation of the DPX-Survivac therapy demonstrating a potentially durable effect of the therapy.
Additionally, patients across all vaccine doses exhibited evidence of desired polyfunctional T cell responses against survivin, a protein that is over-expressed in ovarian cancer and several other tumor types. Statistically significant increases in immune response were achieved with higher doses of DPX-Survivac (p=0.013) and when DPX-Survivac was combined with low dose oral cyclophosphamide (CPA) (p=0.015). A modified vaccination schedule, reducing the dose for the first two vaccinations then boosting with a lower dose every eight weeks, resulted in a lower frequency of local injection related adverse events. Importantly, robust immune responses were produced with the modified immunization schedule, demonstrating the potency and flexibility of DPX-Survivac. Finally, DPX-Survivac was well tolerated with no significant vaccine related systemic adverse events reported.
“With these latest results, we can for the first time point to the fact that the pronounced and persistent survivin-specific T cell immune responses we achieve with DPX-Survivac treatment may translate to a measurable clinical benefit,” stated Dr. Marc Mansour, chief operating officer of Immunovaccine. “This connection between immune response and clinical activity is exciting, particularly since we have demonstrated the ability to generate what we believe are some of the strongest antigen-specific polyfunctional T cell responses reported in a clinical trial.”
The multicenter Phase I/Ib study enrolled 30 stage IIc-IV first-line or recurrent ovarian cancer patients with no evidence of disease progression following chemotherapy. The patients were enrolled across five treatment cohorts to receive various doses of DPX-Survivac (0.1, 0.25 and 0.5 mL) alone or in combination with CPA. A modified vaccination schedule was used in two of the cohorts to evaluate the safety and immune response impact of varying the timing of treatment.
“With our ongoing clinical development efforts, we continue to grow our understanding of the potential role that DPX-Survivac may play in this new cancer immunotherapy environment. In addition to correlating immune response to clinical benefit, this study has offered insight into modulating immune response levels and mitigating adverse events, all through adjusting the vaccine dose and schedule,” said Dr. Mansour. “We are establishing the optimal dosing regimen for future trials including our planned randomized Phase II trial in ovarian cancer.”
In April, Immunovaccine presented positive data from clinical and preclinical vaccine studies, including DPX-Survivac, at the American Association for Cancer Research (AACR) 2014 Annual Meeting. Results demonstrated 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 tumors that could not be treated with vaccine or mCPA alone. The addition of anti-PD-1 checkpoint inhibitor to the DepoVax vaccine/mCPA combination resulted in further enhanced anti-tumor activity, which allowed the treatment of more advanced tumors. The effective tumor regressions that were observed could not be achieved without the use of vaccine or the use of anti-PD-1.
Immunovaccine expects a large randomized 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 are planning to initiate a Phase l/II trial of DPX-Survivac in glioblastoma (brain cancer).