Clinical Trials

DNAtrix’s lead product, DNX-2401 is an oncolytic adenovirus with multiple modifications designed to specifically target a large number tumor cell types without affecting the normal healthy cell. The targeting is achieved by two methods – physical and functional  One, viral protein is modified to recognize tumor cell protein for physical targeting. Two, deletions in the viral genome allows it to replicate effectively in rapidly dividing cancer cells while sparing the more slowly dividing normal cells from damage.

Brain Cancer Study
A Phase I, dose-escalation, two-arm study of DNX-2401 for high grade glioma was initiated in 2009 at the UT MD Anderson Cancer Center (MDACC). Arm A tested direct intratumoral injection of a single dose of DNX-2401 into a growing area of recurrent glioma. Arm B tested intratumoral injection of a divided dose into the resection bed following removal of a recurrent glioma. The A arm study started at 1×107 viral particles (vp) and escalated in half log increments through 3×1010 vp and completed enrollment in April 2012.

There is now compelling evidence that DNX-2401 can i) replicate in human tumors for a period of weeks to months, ii) elicit tumor necrosis within weeks of injection, iii) trigger intratumoral immune cell infiltration and iv) lead to long term tumor destruction detectable by MRI.  Perhaps more importantly, the study agent, DNX-2401was safe and well tolerated in the clinic with no serious product-related toxicities to date.

Ovarian Cancer Study
An investigator-sponsored clinical trial involving the enrollment of 21 patients has taken place at the University of Alabama at Birmingham (UAB) Comprehensive Cancer Center.  The trial was designed to investigate the feasibility and utility of intraperitoneally-administered DNX-2401 for patients with recurrent epithelial ovarian cancer who have persistent or recurrent disease after debulking and paclitaxel/platinum based chemotherapy.  Preliminary clinical findings have underscored the safety of this agent in the human clinical context, as there were no observed adverse events to this point. Initial evaluation of the clinical parameters suggests some of the data trends consistent with clinical response.  Seven of 20 evaluable patients had decrease in CA125 marker from pretreatment values approximately one month after DNX-2401 treatment; four of these patients had a >20% drop in CA125 values.  Significantly, no treatment related serious toxicities were noted and virus transduction to tumor cells was evident, thereby demonstrating the feasibility of this approach. Extensive viral shedding was also absent.

Kimball, K.J., Preuss, M.A., Barnes, M.N., Wang, M., Siegal, G.P., Wan, W., Kuo, H., Saddekni, S., Stockard, C.R., Grizzle, W.E., Harris, R.D., Aurigemma, R., Curiel, D.T., and Alvarez, R.D. (2010) A Phase I Study of a Tropism-Modified Conditionally Replicative Adenovirus for Recurrent Malignant Gynecologic Diseases. Clin Cancer Res 16(21): 5277-87.