CTNI-72. VAL-083 IN PATIENTS WITH RECURRENT GLIOBLASTOMA TREATED UNDER EXPANDED ACCESS PROGRAM

Abstract BACKGROUND Current standard-of-care for glioblastoma (GBM) includes surgery followed by chemoradiation with temozolomide (TMZ) followed by adjuvant TMZ. Almost all GBM patients experience disease progression despite upfront standard-of-care treatment, with a median overall survival of 3-9 months after first recurrence. There are limited treatment options at the time of disease progression, apart from participation in clinical trials. VAL-083 is a bi-functional DNA damaging agent that induces inter-strand DNA cross-links at N7-guanine in a manner independent of O6-methylguanine-DNA-methyltransferase (MGMT). METHODS Under an Expanded Access program (NCT03138629), we used VAL-083 to treat 30 patients with recurrent GBM who were not eligible to participate in clinical trials. Here we report safety and efficacy results. RESULTS Four patients (13.3%) with leptomeningeal disease were excluded from efficacy evaluation. All patients received chemoradiation with TMZ. Twelve (12/26; 46.2%) patients had ≥2 recurrences and 9/26 (34.6%) had prior lomustine. All tumors had ≥1 mutation, with 14/26 (53.8%) having ≥5 mutations; one patient had a hypermutator phenotype. The most common mutations were TERT (57.7%), PTEN (38.5%), TP53 (26.9%), and NF1 (26.9%). All patients started treatment with VAL-083 at 30 mg/m2/day administered on 3 consecutive days every 21 days. Eight (8/26; 30.8%) patients received bevacizumab concurrently with VAL-083. Eight (8/26; 30.8%) patients had a VAL-083 dose reduction. Patients received a median of 3.0 (5-95pth 1-10) VAL-083 treatment cycles. Median progression free survival (mPFS) and median overall survival (mOS) from last disease progression was 5.1 (95%CI: 2.7-7.2) and 9.8 (95%CI: 5.3-16.4) months, respectively. VAL-083 was well-tolerated and the most frequent adverse events were consistent with prior experience, i.e., thrombocytopenia and neutropenia. CONCLUSIONS Use of VAL-083 continues to show benefit in the treatment of GBM patients who have had multiple recurrences and have limited therapeutic options.