DNX-2401: an investigational drug for the treatment of recurrent glioblastoma

ABSTRACT

Introduction: High-grade gliomas (HGG) are extremely aggressive brain malignancies that are fatal. Despite maximal resection, chemotherapy, and radiation, these tumors inevitably recur and present a poor median overall survival (mOS); hence a pressing need for improved treatments.

Areas covered: This review assesses DNX-2401 as a treatment of recurrent HGG. Phase I data on efficacy, safety, and tolerability are examined while insights and perspectives on future directions are offered.

Expert opinion: This phase I study assessed DNX-2401 in two study groups; one received an intratumoral injection without tumor resection while the second received an intratumoral injection followed by surgical resection 14 days later with a second injection into the resection cavity. In patients that did not receive resection, the mOS was 9.5 months while patients in the resection group had a mOS of 13 months, a promising extension of survival compared to historical controls. Furthermore, this study had numerous long-term survivors living for greater than 2 years. DNX-2401 was well tolerated with no Grade 3/4 adverse events; it provoked an immunologic response to the tumor which may contribute to the complete responses in some patients. Randomized-control trials are necessary and further studies are warranted to identify patients who will benefit most.

KEYWORDS:

• DNX-2401
• Delta-24-RGD
• tasadenoturev
• high grade glioma
• glioblastoma
• oncolytic adenovirus

Article Highlights

• DNX-2401 is an oncolytic adenovirus that selectively infects glioma cells after direct injection into the tumor site or resection cavity.

• Early studies of DNX-2401 show potential for prolonging the survival of patients with high-grade glioma.

• Recently published Phase I clinical trial data have shown a modest increase in median overall survival of 13 months in patients that received surgical resection and DNX-2401. Seven patients in the study had a long-term survival of greater than 24 months.

• DNX-2401 was well tolerated with no dose-limiting toxicities and no Grade 3 or greater adverse events.

• DNX-2401 is currently being studied in multiple phase I and II studies as a combination therapy.

• In future trials, it is hoped that there will be a more robust evaluation into the patient and tumor characteristics in partial and complete responders to enhance differentiation and classify which patients will benefit most.

This box summarizes key points contained in the article.

Box 1. Drug summary

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer is a consultant and stockholder of DNATrix, the company that has the rights of DNX2401.

Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded