ACTR-42. CLINICAL TRIALS OF VAL-083 IN PATIENTS WITH CHEMORESISTANT GLIOBLASTOMA

Abstract

Glioblastoma (GBM) is the most common CNS-tumor. Patients with recurrent GBM have few treatment options and dismal prognosis. O6-methylguanine- DNA-methyltransferase (MGMT) is correlated with resistance to standard-of-care treatment with temozolomide and poor patient outcomes. Dianhydrogalactitol (VAL-083) is a bi-functional alkylating agent that readily crosses the blood-brain barrier and has demonstrated MGMT-independent activity in multiple GBM cell-lines and cancer stem cells, in vitro. VAL-083 showed promise against CNS-tumors in prior NCI-sponsored clinical trials. We recently concluded a phase I/II clinical trial studying VAL-083 in recurrent GBM after failing temozolomide and bevacizumab, suggesting potential of VAL-083 to offer clinically meaningful survival benefits and a promising new treatment for GBM patients who have failed or are unlikely to respond to currently available chemotherapeutic regimens. In this phase I/ II trial, VAL-083, 40 mg/m2/day x 3 every 21 days was well tolerated and was selected for study in subsequent clinical trials in GBM. These trials include i) a pivotal, randomized Phase 3 study measuring survival outcomes compared to “physician's choice” control, which, if successful, would serve as the basis for a New Drug Application (NDA) submission for VAL-083. The control arm will consist of a limited number of salvage chemotherapies currently utilized in bevacizumab-failed GBM. ii) A non-comparative, biomarker-driven, Phase 2 study to determine if treatment of MGMT-unmethylated recurrent GBM with VAL-083 improves overall survival at 9 months, compared to reported CCNU control in bevacizumab-naïve patients. iii) A single arm Phase 2 study to confirm the tolerability of DelMar's dosing regimen in combination with radiotherapy and to explore the activity of VAL-083 in newly diagnosed MGMT-unmethylated GBM patients whose tumors are known to express high MGMT-levels. Trial designs and further details will be presented at the meeting. The results of these studies may support a new treatment paradigm in chemotherapeutic regimens for the treatment of GBM.