Ctni-78. evaluation of post-progression treatments after val-083 in recurrent and newly diagnosed gbm mgmt-unmethylated patients

Abstract Almost all GBM patients experience recurrent disease following up-front standard of care treatment, with a median survival of 3-9 months after recurrence. Challenges with salvage therapies include the potential for side-effects, which may limit further treatment. 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 independently of MGMT DNA repair and DNA mismatch repair deficiency. VAL-083 was evaluated in an open-label two-arm biomarker-driven phase 2 trial in MGMT-unmethylated bevacizumab-naïve GBM patients with either recurrent (Group 1) or newly diagnosed GBM requiring adjuvant therapy after chemo-radiation with TMZ (Group 2). Post-progression, patients were followed for survival status, and any post-VAL-083 treatments. Here we review treatments received by patients following participation in this clinical trial, and their outcomes. Patients were excluded from the review if no data had been collected or if they had undergone subsequent surgery. Group 1(n=42) and Group 2(n=31) who received 30 mg/m2 VAL-083 (days 1-3 of 21-day cycle) were evaluated. In Group 1 and Group 2, 17/42 (40.5%) and 20/31 (64.5%), respectively, received an alkylating agent post-VAL-083. Receiving more than the median number of cycles of VAL-083 in either group didn’t limit patients from receiving alkylating agents such as CCNU and TMZ after VAL-083. No hematologic complications were identified. Furthermore, receiving ≥5 cycles of adjuvant TMZ prior to VAL-083 in Group 1 didn’t affect patient’s ability to receive alkylating agents. For both groups, mOS and OS-6 from the last dose of VAL-083 were greater for those receiving alkylating agent post VAL-083, compared to those who didn’t. These data demonstrate that alkylating agents may be administered safely to patients who have progressed following therapy with VAL-083, and patients who have received an alkylating agent after VAL-083 therapy have a better outcome compared to those receiving other treatments.