Tasadenoturev + Pembrolizumab Shows Clinical Benefit in Recurrent Glioblastoma

Glioblastoma with extreme nuclear enlargement.
Glioblastoma with extreme nuclear enlargement.

Updated safety and efficacy data from the fully-enrolled Phase II CAPTIVE / KEYNOTE-192 study of tasadenoturev, also known as DNX-2401, in combination with pembrolizumab (Keytruda®, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co), an immune checkpoint inhibitor used in cancer immunotherapy, for patients with recurrent glioblastoma shows clinical benefit.

Glioblastoma is one the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. Tasadenoturev, an investigational oncolytic adenovirus developed by DNAtrix, a privately held, clinical stage, biopharmaceutical company, has been granted PRIME and Orphan designation by the European Medicine Agency (EMA), and Fast Track and Orphan designation by the U.S. Food and Drug Administration (FDA).

Favorable safety
The data, presented at the annual meeting of the Society for NeuroOncology (SNO) held November 22-24, 2019 in Phoenix, Arizona, demonstrated that the combination of tasadenoturev and pembrolizumab elicits durable clinical activity and has a favorable safety profile.

As part of the trial, a total of 48 patients with recurrent glioblastoma were treated at 15 participating clinical sites with the regimen of tasadenoturev, followed by pembrolizumab.

Clinical trials
The CAPTIVE / KEYNOTE-192 is a Phase II multicenter study evaluating a single intratumoral injection of tasadenoturev followed by standard dosing with pembrolizumab every three weeks for up to two years – or until disease progression – to determine the safety and efficacy in patients with recurrent glioblastoma and gliosarcoma. The trial is sponsored by DNAtrix and Merck Sharp & Dohme.

Trial design
The majority of patients experienced clinical benefit following treatment, including durable complete and partial responses. Interim median overall survival for patients is currently 12.3 months. In addition, the interim safety analysis demonstrates that the therapy has a positive benefit-risk profile, there were no unanticipated adverse events and patients remained on pembrolizumab for a median of 5.5 months with a maximum of 34 cycles.

Clark C. Chen, MD, Ph.D, is a nationally recognized brain tumor researcher and surgeon, with a dedicated interest in understanding how glioblastoma acquires resistance to radiation and chemotherapy. He is a National Institutes of Health (NIH) RO1-funded investigator whose research focuses on developing novel diagnostic and therapeutic approaches for brain tumor patients. He is also a leader in the study of DNA repair and gene therapy in brain tumors. Chen is the recipient of several highly competitive research awards, including the Damon Runyon Fellowship Award, the Sidney Kimmel Scholar Award, the Burroughs Wellcome. Photo courtesy: The University of Minnesota.

“The data hold great promise for patients afflicted with glioblastoma, the most common form of adult brain cancer,” said said Clark C. Chen, MD, Ph.D, Professor, Lyle French Chair in Neurosurgery and Department Head at the University of Minnesota.

“Glioblastoma is a disease associated with near uniform fatality. In this context, the trial results are striking,” Chen added, who presented the results of the CAPTIVE / KEYNOTE-192 study.

“The results suggest that the combination of tasadenoturev and pembrolizumab has the potential to revolutionize the care of glioblastoma patients. I look forward to the rigorous studies aimed to validate the efficacy of this investigational agent,” Chen added.

Significant milestone
“These interim data from the CAPTIVE / KEYNOTE-192 trial are a significant milestone for us in the development of tasadenoturev as an innovative treatment for glioblastoma,” noted Frank Tufaro, Ph.D, Chief Executive Officer of DNAtrix.

DNAtrix’s lead product, tasadenoturev, also known as is DNX-2401, is a modified common cold virus that selectively targets and kills cancer cells. In clinical trials, the investigational drug has demonstrated a potent anti-tumor mechanism of action by (1) replicating in human tumors (2) eliciting tumor necrosis and (3) triggering an immune response.
DNAtrix’s lead product, tasadenoturev, also known as is DNX-2401, is a modified common cold virus that selectively targets and kills cancer cells. In clinical trials, the investigational drug has demonstrated a potent anti-tumor mechanism of action by (1) replicating in human tumors (2) eliciting tumor necrosis and (3) triggering an immune response. Photo courtesy: DNAtrix.

.”[…]. the data suggest that tasadenoturev has a superior clinical benefit and safety profile compared to currently approved chemotherapy for recurrent glioblastoma, and we are particularly pleased that, together with pembrolizumab, tasadenoturev elicited a number of robust and durable antitumor responses,” Tufaro added.

Mechanism of Action
Tasadenoturev, an oncolytic adenovirus, is a modified common cold virus that selectively targets and kills cancer cells. The investigational drug is specifically engineered to infect, replicate in, and kill cancer cells to elicit an immune response. In more than a decade of scientific and clinical research, including clinical studies across several tumor types, tasadenoturev has shown to be safe and effective.

Clinical trials
– Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects (CAPTIVE / KEYNOTE-192) – NCT02798406

Reference
[1] Wirsching HG, Galanis E, Weller M. Glioblastoma. Handb Clin Neurol. 2016;134:381–397. doi:10.1016/B978-0-12-802997-8.00023-2