CTNI-36. SINGLE INSTITUTE REPORT OF DORDAVIPRONE (ONC 201) PLUS BEVACIZUMAB COMBINATION THERAPY ON THE EXPANDED ACCESS PROTOCOL (ONC 028)

Abstract BACKGROUND Dordaviprone (ONC201), an oral, CNS penetrant, targeted small molecule ClpP agonist and DRD2 antagonist, is currently under investigation in patients with H3K27M-mutant diffuse glioma. Expanded access programs (EAPs) have offered a means to gain real-world experience with dordaviprone ahead of potential regulatory approval. Here we describe our experience implementing the combination of bevacizumab and dordaviprone in this EAP setting. METHODS ONC028, the dordaviprone EAP protocol in the US, was designed to provide access for patients that were ineligible for dordaviprone clinical trials. We retrospectively analyzed clinical features and treatment experience of 16 patients receiving dordaviprone (625 mg once weekly) plus bevacizumab as part of ONC028 at Providence/St. John’s Cancer Institute. RESULTS Patients ranged in age from 20-59 years. Patients treated with combination dordaviprone + bevacizumab remained on dordaviprone therapy for an average of 7.5 months, 4 patients remain on dordaviprone with follow up time ranging from 6-29 months as of the data cutoff. The combination therapy did not result in any additional reported side effects outside of those anticipated from each agent as monotherapy. No deterioration in quality of life was observed in patients receiving the combination. CONCLUSIONS This single-center experience provides insight into the safety and treatment duration associated with the combination of dordaviprone and bevacizumab in real-world patients enrolled in ONC028. No negative impact on quality of life was reported with combination therapy. The side effect profile of the combination therapy did not reveal any increased toxicity. These data highlight a potential role for the addition of bevacizumab during dordaviprone treatment.