The open-label Phase 1b trial (NCT02785250) is evaluating the safety and efficacy of Immunovaccine’s lead candidate DPX-Survivac in combination with Incyte’s IDO1 enzyme inhibitor epacadostat and low-dose cyclophosphamide in about 40 patients with recurrent ovarian cancer.
DPX-Survivac consists of small fractions of the survivin protein, which are able to trigger an immune response. DPX-Survivac is thought to work by eliciting a toxic T-cell immune response against cells presenting survivin peptides.
Survivin, seen as a promising tumor-associated antigen, is broadly over-expressed in most cancer types and promotes tumor growth. It plays an essential role in supporting tumor blood vessel growth and promoting resistance to anti-cancer therapies.
Epacadostat is a potent, selective oral inhibitor of IDO1, an enzyme expressed in many cancers that suppresses T-cell response.
The study’s Phase 2 part will include up to 32 additional patients and also be open label, meaning all enrolled will receive the treatment. Its goal, the companies said in a press release, will be to evaluate the clinical contribution of each investigational therapy in the combination treatment.
The Phase 1b study is taking place five sites in the U.S. and in Ontario, Canada, and recruiting patients. More information is available here.
Data reported from a first group of 10 patients treated in Phase 1b show that the combination regimen — DPX-Survivac, epacadostat at 100 mg and low-dose cyclophosphamide— showed a 70 percent disease control rate, including partial response in three of these patients, or 30 percent. A tolerable safety profile was also seen in this data, reported in December.
Blood tests also indicated that most treated patients showed a targeted T-cell activation, which correlates with tumor regression.
At the time of data cut-off, preliminary data on three patients in a second dosing group — receiving 300 mg epacadostat twice-daily, DPX-Survivac, and low-dose cyclophosphamide — found that one patient experienced tumor regression of 25% and two patients had stable disease.
Patients in this second group are still undergoing dosing, and updates are expected by the close of June.
“We were encouraged by the topline data we shared last December from the first dosing cohort of our trial, especially in this hard-to-treat population of ovarian cancer patients,” Frederic Ors, chief executive officer at Immunovaccine, said in the release. “We believe that these results further support the hypothesis that the unique mechanism of action underscoring our T cell activation technology can trigger tumor regressions, even in patients who typically don’t respond well to current monotherapies.”
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 also has received orphan drug status from the FDA and the European Medicines Agency (EMA) for the same indication.