Abstract LB126: RELA fusion-positive ependymoma and diffuse midline glioma treated with VAL-083 under expanded access - case reports
Authors: Kamiya-Matsuoka Carlos , Knight Stephanie , Hanna Teresa , Gregory Timothy A. , Langlands John , Brown Dennis , Puduvalli Vinay K. 
Published: April 2023

Abstract
Ependymoma can occur anywhere in the central nervous system (CNS), but often occurs near the ventricle of the brain and central canal of the spinal cord. Ependymoma accounts for 5.7% of all childhood and 1.9% of all adult CNS tumors. RELA fusion-positive ependymoma is a subgroup associated with supratentorial location, higher WHO grade and worse prognosis. Diffuse Midline Glioma (DMG) is another relatively rare CNS tumor, originating in the midline locations of the brain (including thalamus, pons and spinal cord), accounting for 10% of all childhood and less than 4% of adult CNS tumors. For ependymoma standard treatment includes surgery and radiation therapy, with limited systemic options other than clinical trials for recurrent disease. For DMG, surgical intervention is restricted to biopsy, with radiation as standard therapy. Systemic options for both ependymoma and DMG are limited.VAL-083 is a bi-functional DNA-targeting agent which rapidly induces inter-strand DNA cross-links at N7-guanine inducing double-strand breaks causing cell death and acts independent of MGMT DNA repair and H3F3 K27M mutation status in high-grade gliomas. We report on 2 patients: one with ependymoma and one with DMG, treated with VAL-083 under an expanded access program. Both patients had recent disease progression and limited therapeutic options. Case #1: a 47-year-old male who was diagnosed with a left parietal high grade (3) anaplastic ependymoma and with IDHwt and unmethylated MGMT promoter status. Inter- and intragenic fusion analysis of tumor tissue revealed RELA fusion-positive ependymoma. He had undergone 2 resections and had received radiation and multiple systemic treatment regimens. Case #2: a 21-year-old male who was diagnosed with DMG of the brain stem, with IDHwt and unmethylated MGMT promoter status. He had undergone radiation therapy, and multiple treatment regimens. Both patients were not eligible to participate in any clinical trial and received VAL-083 under an expanded access program. They initiated treatment with VAL-083 (30 mg/m2 for 3 consecutive days every 21 days) and have completed 3 cycles. Both are neurological and radiological stable, they continue to receive VAL-083. No adverse events have been reported and no dose reductions have been required. These cases highlight that VAL-83 may be a treatment option for recurrent RELA fusion-positive ependymoma and DMG refractory to other treatment regimens. Additional safety and efficacy outcomes related to patient status will be presented at the meeting.Clinicaltrials.gov Identifier: NCT03138629. The treatment plans for this EAP patient were approved by MD Anderson Cancer Center IRB.
Citation Format: Carlos Kamiya-Matsuoka, Stephanie Knight, Teresa Hanna, Timothy A. Gregory, John Langlands, Dennis Brown, Vinay K. Puduvalli. RELA fusion-positive ependymoma and diffuse midline glioma treated with VAL-083 under expanded access - case reports [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB126.