Novel immunotherapy ‘cocktail’ shows promise in ovarian cancer clinical study

HALIFAX, Nova Scotia—Immunovaccine Inc., a clinical stage vaccine company, has announced that new positive clinical data on the company’s lead cancer vaccine candidate, DPX-Survivac, was to be presented as a poster at the 2014 ASCO Annual Meeting in Chicago, IL from May 30 to June 3. Results presented from the Phase 1/1b clinical study demonstrate promising early evidence of clinical activity for DPX-Survivac in ovarian cancer patients, including one patient who experienced a partial response (PR). The PR, defined as a shrinking of tumor size by at least 30 percent, using Response Evaluation Criteria In Solid Tumors (RECIST 1.1), was accompanied by reduction in levels of a commonly used ovarian cancer biomarker (CA125) and a significant increase in vaccine-induced immune responses.

Highlights from the abstract include the observation that one study patient with residual disease following platinum therapy experienced a PR which correlated with robust immune responses to DPX-Survivac. The PR persisted following discontinuation of the treatment. The authors noted that target immune responses were seen across all doses and when DPX-Survivac was administered alone or with low dose oral cyclophosphamide (CPA). Statistically significant increases in immune response were seen with higher doses of DPX-Survivac and when DPX-Survivac was combined with CPA. DPX-Survivac was well tolerated with no significant systemic adverse events reported.

“The durable clinical response highlights the therapeutic potential of DPX-Survivac,” stated Dr. Marc Mansour, chief operating officer of Immunovaccine. “To our knowledge, the target immune responses induced by our vaccine approach are among the strongest of any published immune results in the cancer immunotherapy field.”

Mansour notes that the problem with vaccines has been that they don’t work well enough on their own. He believes that combination therapies may hold the answer. “We were looking for immune modulators. Low dose cyclophosphamide seems to enhance the immune system and make tumors more susceptible to attack.” The addition of a checkpoint inhibitor such as PD-1 adds a third mechanism of action to the anti-cancer cocktail.

“All cancers are affected by T-cells. The more they are, the longer you live,” Mansour observes. “Checkpoint inhibitors take the brakes off the immune system with a significant minority of patients. The key is to find the right combination to help the majority of patients.” This approach has helped transform HIV/AIDS into a chronic, treatable disease,” Mansour notes, and he believes it can work with cancer as well.

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 (on and off dosing) cyclophosphamide (mCPA), an immune modulating agent, enhanced the immunogenicity of DepoVax-based vaccines in preclinical cancer models consistent with previously reported Phase 1 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 2 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 1/2 trial of DPX-Survivac in glioblastoma (brain cancer) with the first patient receiving the vaccine in 2014.

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.

DPX-Survivac consists of survivin-based peptide antigens formulated in the DepoVax adjuvanting platform. Survivin has been recognized by the National Cancer Institute as a promising tumor-associated antigen (TAA) because of its therapeutic potential and its cancer specificity. Survivin is broadly over-expressed in solid tumors and blood cancers including ovarian, breast, colon and lung cancers, among others. Survivin plays an essential role in antagonizing apoptosis, supporting tumor-associated angiogenesis, and promoting resistance to various anti-cancer therapies. Survivin is also a prognostic factor for many cancers and it is found in high percentage of cancer patients.

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 actively search for tumor cells expressing survivin and destroy them.

Immunovaccine Inc. develops cancer immunotherapies and infectious disease vaccines based on the company’s DepoVax platform. Immunovaccine has advanced two T cell activation therapies for cancer through Phase 1 human clinical trials. Its lead cancer vaccine therapy, DPX-Survivac, is expected to enter Phase 2 clinical studies in 2014 in ovarian cancer and glioblastoma (brain cancer). The company is also advancing an infectious disease pipeline including innovative vaccines for respiratory syncytial virus (RSV) and anthrax.