DPX-0907 is a unique multi-targeted therapeutic cancer vaccine designed to train the immune system to recognize and attack cancer cells. The immunotherapy combines seven tumor associated antigens (TAAs) with Immunovaccine’s novel DepoVax adjuvanting delivery platform, allowing for the creation of a depot effect upon vaccination that presents the antigens and adjuvant to the immune system for a prolonged period of time.
Treatment with DPX-0907 is designed to train the body’s T cells, sophisticated white blood cells that play a key role in fighting cancer, to recognize the antigens incorporated into the vaccine. In doing so, the T cells become programmed to specifically target and attack cancer cells, while leaving normal healthy cells unharmed. By incorporating multiple target antigens, DPX-0907 attempts to attack cancer cells through multiple avenues and potentially minimize the cancer cells’ demonstrated ability to edit and escape the impact of individual antigens.
DPX-0907 has successfully completed a Phase I clinical study that generated positive results in the areas of safety, tolerability and immune response. The study met its primary objective of safety with overall results demonstrating that DPX-0907 is generally well tolerated by all patients and is considered safe at both dose levels with no vaccine related serious adverse effects reported. The study also met its secondary endpoint, demonstrating antigen-specific CD8+ T cell responses following vaccination. These safety and immunogenicity findings validate the proprietary DepoVax liposome-in-oil platform, which is designed to augment vaccine antigens by incorporating adjuvants and other vaccine enhancement features while simplifying the use of oil-based depot vaccines, through an emulsion-free approach.
Important findings from the trial included:
- 61 percent (11/18) of the evaluable cancer patients, and 89 percent (8/9) of the evaluable study patients with breast and ovarian cancer, experienced the desired targeted T cell responses against one or more of the seven key cancer-specific antigens contained in DPX-0907.
- In a majority of responding patients, the antigen-specific T cells triggered by DPX-0907 treatment secreted multiple type 1 cytokines, indicating the T cells possess the polyfunctional activity that has been increasingly associated with host protection in preclinical vaccine and tumor immunotherapy models. This finding suggests that DPX-0907 may be generating clinically-relevant immune responses and that the selected cancer-specific antigens have been combined with a suitably immunogenic delivery mechanism.
- 82 percent (9/11) of the study’s responders experienced at least a two-fold increase in the frequency of antigen-specific, cytokine secreting CD8+ T cells compared to baseline, with eight of those patients showing antigen-specific CD8+ T cells that produced more than one cytokine simultaneously. These findings illustrate DPX-0907’s potential in generating a meaningful therapeutic response as CD8+ T cells are the cytotoxic T cells responsible for destroying tumor cells.
- 73 percent of the study’s immune responders generated a response following the first vaccination suggesting favorable immune induction potential for DPX-0907 and 64 percent maintained a persistent response at one month following a third vaccination.
- When analyzing the results in breast and ovarian cancer specifically, 56 (5/9) percent of these patients generated an immune response following the first vaccination, with the immunological response rate increasing to 89 (8/9) percent after three vaccinations. This compares favorably with other clinical trials testing therapeutic vaccines in breast and/or ovarian patients with a similar disease profile.
- In addition to antigen-specific CD8+ T cell responses, CD4 responses against a T helper peptide included in the vaccine were also detected. The CD4 responses correlated with antigen-specific CD8+ T cell responses in the same assay, supporting the hypothesis that the CD4 responses may have facilitated the generation of the specific CD8+ T cells observed. The CD4 or “helper” epitope, which was included in the vaccine to assist in the activation of CD8+ T cells, constitutes an important vaccine feature included in DPX-0907.
- A key association between the achievement of immune responses during the study and the patients’ level of disease burden was demonstrated. A detailed analysis showed that the different study patient populations possessed key differences, namely that the breast and ovarian cancer patients had responded favorably to previous treatments (stable disease or complete response), whereas the majority of prostate cancer patients presented with late stage (Stage IV) disease and rising prostate specific antigen (PSA) levels even though they had all undergone at least three previous treatments. These dynamics, combined with the fact that advanced ovarian and breast cancer patients had high immune response rates while advanced prostate cancer patients had lower immune response rates, suggest that patients with a history of favorable responses to therapy, and in a state of minimal residual disease, are likely preferred candidates for DPX-0907 immunotherapy. These findings support the belief that DPX-0907 holds therapeutic potential in treating properly selected patients with either ovarian, breast or prostate cancer.
The completed DPX-0907 Phase I trial was an open-label, dose-escalation trial conducted at five centers in the U.S. with patients receiving three injections (0.25 mL or 1 mL doses) of the active immune therapy DPX-0907, three weeks apart. Safety was assessed in eleven patients in the 0.25 mL dose group and eleven patients in the 1 mL dose group. The immunogenicity results were based on an analysis of nine evaluable patients in the 0.25 mL dose group and nine evaluable patients in the 1 mL dose group.