DNX-2401 is an oncolytic immunotherapy being investigated by DNAtrix for the treatment of cancers, especially brain tumors. Oncolytic viruses, infect and destroy cancer cells while leaving normal cells intact.

Pre-clinical data has shown that DNX-2401 fights cancer by triggering the infiltration of immune cells inside the tumor and can lead to their long-term destruction.

The treatment also has been well-tolerated in patients with recurrent glioblastoma, a devastating primary brain tumor resistant to conventional therapies and the second most common cause of death from brain disease.

How DNX-2401 works

DNX-2401 was designed to yield high potency and safety. To achieve these two requirements, it was engineered by modifying the genome of an adenovirus. The modified virus can replicate within tumor cells, but not normal cells. DNX-2401 also can spread between cancerous cells, causing a chain reaction of tumor elimination and destruction. This process also triggers an immune response against the tumor, which is essential in the treatment of cancer.

DNX-2401 in clinical trials

Clinical trials involving DNX-2401 have been completed or are underway to investigate its anti-tumor activity.

For example, safety, overall recurrence, and overall survival in glioma patients treated with DNX-2401 in combination with Temodal (temozolomide), a drug used to treat certain types of brain tumors, were investigated in a Phase 1 clinical trial (NCT01956734).

The results of this trial were published in the scientific journal Cancer Research and demonstrated that the combination of the two treatments was well-tolerated and showed therapeutic activity. The study, which is now complete, showed that the combination was effective in killing glioblastoma tumor stem cells and tumors derived from them, leading to prolonged survival when compared to other therapies.

A Phase 1b study (NCT02197169) evaluating the safety and effectiveness of DNX-2401 as monotherapy, or followed by treatment with Actimmune (interferon gamma-1b). Actimmune is a drug that inhibits the proliferation of normal and malignant cells in adults diagnosed with glioblastoma who have experienced disease progression after receiving initial treatment. The purpose of this study is to evaluate how well  recurrent glioblastoma or gliosarcoma tumors respond to DNX-2401 administered directly into the brain tumor, where it may establish an active infection by replicating inside tumor cells. The trial is ongoing in Florida, Ohio, and Texas but no longer recruiting participants.

Similarly, a Phase 2 multicenter, open-label study (NCT02798406) is being conducted to evaluate the safety and effectiveness of DNX-2401 in combination with Keytruda (pembrolizumab). The main purpose of this study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor respond to DNX-2401 followed by intravenous (into the bloodstream) administration of Keytruda every three weeks for up to two years, or until disease progression. Keytruda is an immune checkpoint inhibitor known to activate T-cell-mediated immune response against tumor cells. The study, which is currently recruiting participants in the U.S. and Canada, is expected to be completed by mid-2020.

DNAtrix also is planning a Phase 3 study to investigate DNX-2401 as a monotherapy for glioblastoma patients.

Other details

DNX-2401 has been granted fast track and orphan drug designation by the U.S. Food and Drug Administration (FDA) because of its anti-tumor activity and the promising results that it has shown in treating cancer.


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