Clinical Trials

Date: 2017-03-29

Type of information: Interim results

phase: 1b

Announcement: interim results

Company: Immunovaccine Technologies (Canada) Incyte (USA - DE)

Product: DPX-Survivac with epacadostat (INCB24360) and low-dose cyclophosphamide

Action mechanism:

• peptide/enzyme inhibitor/immunotherapy product. 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 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. It 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.
• Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity. Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer types.
• DPX-Survivac is designed to activate the T cells of the immune system to recognize survivin-expressing cancer cells. Epacadostat, on the other hand, is designed to inhibit IDO1-mediated immune suppression in the tumor microenvironment. Thus, co-administering these immunotherapies may lead to enhanced anti-tumor effects by both activating the immune system to recognize the cancer, and simultaneously lessening suppression of the immune response.

Disease: recurrent ovarian cancer

Therapeutic area: Cancer - Oncology

Country: Canada, USA

Trial details:

• The Phase 1b company-sponsored clinical trial is a single-arm, open-label study of patients who have been diagnosed with platinum-resistant and sensitive ovarian cancer, and who have completed first-line treatment with measurable disease. Investigators plan to enroll up to 40 participants at up to ten sites in the U.S. and Canada.
• The study’s primary objective is to assess the safety and immunogenicity of the treatment, and to determine changes in the immune cell infiltration into tumors.
• Secondary objectives include objective response rate, duration of response, and time to progression. Investigators are evaluating patients over a 12-month treatment schedule, collecting biopsy and blood samples before and after treatment. In addition, investigators are performing CT scans at the outset for each patient, repeating the scans every two months to evaluate status of the disease and to assess potential clinical benefit. In addition to the early findings related to disease progression and the presence of survivin-antigen specific CD8+ T cells in the blood, analysis of the tumor revealed increases in multiple T cell markers, including cytotoxic markers and checkpoint inhibitor molecules.
• This triple combination study is the result of a collaboration between Immunovaccine and Incyte Corporation to assess the safety and effectiveness of DPX-Survivac, along with epacadostat and low-dose cyclophosphamide in patients with recurrent ovarian cancer who have measurable disease.
• Resulting from a collaboration between Immunovaccine and Incyte, the Phase 1b clinical trial will assess the safety and effectiveness of Immunovaccine’s novel T cell activating therapy, DPX-Survivac, along with Incyte’s investigational oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, epacadostat (INCB24360), and low-dose cyclophosphamide in patients with recurrent ovarian cancer who have measurable disease. Incyte co-funded the trial under the terms of the agreement between the two companies, by Q2 2016. (NCT02785250)

Latest news:

• • On March 29, 2017, Immunovaccine announced the first interim data analysis from its ongoing Phase 1b clinical study of its novel T-cell activating immuno-oncology candidate, DPX-Survivac, in combination with epacadostat and low-dose cyclophosphamide. The analysis included the results of blood tests, tumor biopsies and CT scans to assess safety, disease progression and T-cell response for the first four evaluable patients in the trial.
• All patients enrolled in the trial have recurrent ovarian cancer with evidence of progressive disease. Based on the interim analysis, the combination therapy appears to have an acceptable safety profile, with a single grade 3 and single grade 4 event reported and no serious adverse events (SAEs) reported. At the time of the interim analysis, three of four patients exhibited stable disease, while a fourth patient continued to progress and discontinued the trial. In addition, researchers observed: • Signs of increased T cell activity in tumors in three of the four patients based on RNA sequencing • Stable disease with signs of tumor shrinkage in the patient who has been in trial for the longest duration thus far (based on CT scan at day 140) Immunovaccine expects to complete enrollment and issue topline data by the end of 2017. Patients interested in enrolling in this trial can find more information via clinicaltrials.gov.
• • On August 25, 2016, Immunovaccine announced new data from its Phase 1/1b trial in ovarian cancer. These data from the Phase 1/1b trial yielded positive findings on tumor clinical response—including the presence of relevant circulating T cells and increased expression of several checkpoint inhibitor molecules. New analyses from the trial indicated: • Targeted T cell responses to survivin, the DPX-Survivac target protein, were observed in 87 percent of study participants evaluable for immune response (47 of 54 evaluable patients) • Of participants in this trial who generated T cell responses, 79 percent (37 of 47 patients) were able to maintain durable immune responses sustained over time with repeated DPX-Survivac injections. • While the study was not designed to assess progression-free survival (PFS), it was observed in the extended follow-up that, of the 18 participants who completed the three doses of the Phase 1 study, 50 percent achieved at least 24 months progression-free survival from the end of their last chemotherapy, with three participants being free for more than five years since their last treatment. (Historical progression-free survival in ovarian cancer is 10 to 12 months for first-line treatment and 6 to 8 months for second-line treatment). • Additional blood and tumor analysis performed on one participant showed increased levels of expression of several inhibitory checkpoint molecules after DPX-Survivac treatment • Researchers concluded an optimal dosing schedule for upcoming clinical studies involving DPX-Survivac in ovarian cancer, consisting of two ‘priming’ injections with a booster administered every eight weeks over the duration of up to one year of treatments.
• This analysis follows the completion of enrollment and dosing in Immunovaccine’s open-label, dose-ranging Phase 1/1b program evaluating the safety and immunogenicity of its lead immuno-oncology drug candidate, DPX-Survivac in participants with stage IIc-IV ovarian cancer. Eight cohorts of patients received different doses and schedules of subcutaneous injections of the DPX-Survivac vaccine together with or without low doses of metronomic cyclophosphamide. In total, 56 high-risk participants with epithelial ovarian cancer after first or second line chemotherapy received DPX-Survivac in the study, which was conducted across multiple sites in the U.S. and Canada. As previously published, a trial participant with stable but measurable disease also achieved a partial response (PR) as measured by Response Evaluation Criteria In Solid Tumors (RECIST 1.1). The subject experienced a 43 percent tumor shrinkage and progression-free survival interval of 16 months from end of last chemotherapy treatment, during which time she received DPX-Survivac therapy. Immunovaccine plans to continue collecting long-term safety and progression-free data, even though the trial was not designed specifically to assess PFS or not placebo controlled, and is not powered to definitively conclude on long-term outcomes.
• • On January 11, 2016,  Immunovaccine announced  the FDA and Health Canada clearance to initiate a clinical study of DPX-Survivac in combination with low-dose cyclophosphamide and epacadostat. Under the approved protocol, the Phase 1b clinical trial will be a single arm, non-randomized, open label, uncontrolled, safety and effectiveness study that will enroll up to 32 participants at up to six sites in the U.S. and Canada. The primary objective is to determine the safety and immunogenicity (the ability to produce an immune response) of the treatment, and to determine changes in the immune cell infiltration into tumors. Secondary objectives include objective response rate, duration of response and time to progression.

Is general: Yes