Patients with a certain type of lymphoma whose tumors are expressing the survivin protein may be able to participate in a Phase 2 Canadian clinical trial of Immunovaccine‘s cancer vaccine DPX-Survivac.
The vaccine will be administered with an immune checkpoint inhibitor and low-dose cyclophosphamide to patients with measurable or recurrent diffuse large B-cell lymphoma (DLBCL). The idea for the three-therapy study grew out of a two-therapy U.S. trial of DPX-Survivac.
Immunovaccine will begin enrolling patients for the new trial after regulatory clearance from Health Canada.
“While immunotherapies, such as checkpoint inhibitors, are rapidly changing the standard of care in many cancers, it has been reported that only about 20 percent of patients are able to respond to these therapies alone, leaving the vast majority of patients with a significant unmet medical need,” Frederic Ors, chief executive officer of Immunovaccine, said in a press release.
“Our clinical strategy builds on our earlier research, which indicated that novel combination immunotherapies—particularly those with the ability to increase T-cell tumor infiltration—may work together synergistically to increase the number of patients responding to today’s advanced treatments,” he added. “We remain committed to working with world-class partners to bring these combinations through clinical development. Our goal is to generate more therapeutic options for patients currently underserved in today’s treatment landscape.”
DPX-Survivac is designed to provoke a strong immune response toward cancer cells expressing survivin. High levels of the protein are found in 60 percent of DLBCL patients and in those with several other cancers.
The U.S. food and Drug Administration has granted fast track status to DPX-Survivac as a maintenance therapy in advanced ovarian cancer. The FDA and European Medicines Agency have also designated in an orphan drug, which will accelerate its approval process.
A Phase 2 U.S. clinical trial (NCT02323230) started by testing a combination of DPX-Survivac and a low-dose cyclophosphamide for treating DLBCL. But results in December 2016 from the first two patients dosed suggested that adding an immune checkpoint inhibitor could increase DPX-Survivac’s punch.
The original two-drug combo did increase the number of T-cells in tumors, meaning a stronger immune response was occurring. But the team also discovered high tumor-cell levels of a protein that was likely limiting the T-cells’ punch.
The solution was to add another compound to the combo that could prevent the PD-L1 protein from thwarting the T-cells, they decided. That would be either an anti-PD-1 or anti-PD-L1 agent.
The Canadian trial will cover the three-drug combo that researchers suggested. The new non-randomized, open-label trial will have 25 participants at five centers. It will assess the effectiveness and safety of adding a checkpoint inhibitor to the DPX-Survivac and cyclophosphamide mix.