CTNI-32. PHASE 2 STUDY OF VAL-083 AND RADIOTHERAPY IN NEWLY DIAGNOSED MGMT-UNMETHYLATED GBM

Abstract VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand cross-links at N7-guanine, leading to double-strand breaks and cell death. In vitro in vivo studies have demonstrated circumvents MGMT-mediated chemoresistance differentiates it from other therapies used the treatment of GBM, including temozolomide (TMZ). also acts as radiosensitizer against GBM cancer stem cells vitro. A Phase 2 study was conducted evaluate safety tolerability when administered concurrently with radiation therapy (RT) newly diagnosed MGMT unmethylated GBM. Stage 1 dose-escalation phase confirm dose this setting. Patients received 20, 30, or 40 mg/m2/day x 3 days every 21 combination standard (2 Gy/day, 5 days/week for 6 weeks). an expansion enroll up 20 additional patients 30 RT. total 29 were enrolled completed treatment, 25 receiving VAL-083. The median number cycles by all 9 (range 2-13). Consistent our prior experience, myelosuppression most common adverse event. Pharmacokinetics (Cmax AUC) broadly linear respect dose, drug half-life 0.8 hrs. sub-group patients, levels CSF found be least high those plasma. progression free survival (PFS) 9.3 (95%CI: 6.4-12.0) months. Eighteen (18/29; 62.1%) died, overall 19.6 14.0-22.4) These results support potential benefit alternative tumors resistance TMZ. Clinicaltrials.gov: NCT03050736.