DPX-Survivac combined with intermittent low-dose cyclophosphamide can generate significant anti-tumor immune responses that correlate with tumor regression in women with recurrent advanced ovarian cancer, latest results from the DECIDE1 Phase 2 trial show.
Interim data announced by DPX-Survivac‘s developer, IMV, revealed that all 15 patients with smaller tumors (less than 5 cm at the study’s start) experienced some level of clinical benefit from the combo treatment. This confirms prior Phase 1 findings demonstrating that smaller tumors had better responses to the combined treatment.
Among these patients, four had their tumors regress enough to be considered a partial response, and remained without signs of disease progression over a significant period of time, researchers said.
DECIDE1’s most recent results are being presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31-June 4 in Chicago, in a poster titled “DPX-Survivac and intermittent low-dose cyclophosphamide (CPA) with or without epacadostat (E) in the treatment of subjects with advanced recurrent epithelial ovarian cancer (DeCidE1 trial): T cell responses and tumor infiltration correlate with tumor regression.”
DPX-Survivac is an investigational immunotherapy designed to activate T-cells and boost their ability to recognize and attack cancer cells, specifically those that have at their surface a protein called survivin.
Survivin is a protein that is overproduced in more than 20 solid and blood cancers. It plays an important role in tumor progression, supporting its survival and growth. It is also associated with more aggressive cancers and their resistance to chemotherapy. Thus, the protein is seen as a promising tumor-associated antigen, with the potential to elicit effective anti-cancer immune responses.
The new therapy consists of small fragments of survivin protein formulated in IMV’s proprietary DPX drug delivery platform. It is administered as an injection under the skin, and is intended to induce a long-lasting activation of cytotoxic T-cells against survivin-expressing cancers. This is expected to halt tumor proliferation, elicit tumor cell death, and lead to lasting tumor regressions, IMV said in a press release.
DECIDE1 Phase 1/2 trial (NCT02785250) was initially planned to evaluate a combination of DPX-Survivac, epacadostat (a checkpoint inhibitor in development by Incyte), and low-dose cyclophosphamide for ovarian cancer patients whose cancer came back after surgery and at least one chemotherapy regimen.
Earlier results from the Phase 1b part led IMV and Incyte to stop dosing patients with epacadostat. Still, the trial continued to study the effects of combining DPX-Survivac and cyclophosphamide in the Phase 2 part.
The Phase 1b part included 53 patients, and showed that the combo treatment was well-tolerated and induced the expansion of survivin-targeting T-cells, meeting the trial’s main goal for that part. Researchers also found that lasting responses correlated with the number of T cells within tumors and that women with smaller tumors had better responses to treatment.
Preliminary results from the Phase 2 part of the study, which has enrolled 12 patients so far, continue to demonstrate the clinical benefit of combining DPX-Survivac and intermittent low-dose cyclophosphamide, with or without epacadostat.
Data show that the infiltration of survivin-specific T-cells into the tumors correlates with tumor regression. All patients with tumors of less than 5 cm have shown clinical benefits. Four even reached a partial response and remained without progression “over a prolonged period,” researchers said.
“The treatment studied leads to strong survivin-specific T-cell responses. Infiltration of tumors by survivin-specific T cells correlated with clinical benefit in treated subjects,” the team said.
They are now exploring the use of a predictive model based on tumor size to improve response to DPX-Survivac therapy.
DPX-Survivac was granted fast track designation by the U.S. Food and Drug Administration (FDA) as maintenance therapy in advanced ovarian cancer in 2014. It has also received orphan drug status from the FDA and the European Medicines Agency (EMA) for the same indication.