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

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.