A Phase 2 biomarker driven, Study of DB107, a Retroviral Replicating Vector, Combined With 5-FC in Patients with Recurrent Glioblastoma or Anaplastic Astrocytoma

PROJECT SUMMARY High-grade gliomas are the most common primary brain tumors in adults that continue to have poor median 5-year survival rates despite maximal safe resection and chemoradiation. Over the last 20-years, the standard treatment for high-grade gliomas has not changed drastically; therefore, attention has shifted to

developing virotherapies to improve outcomes from this lethal disease. Viral based gene therapies are preferred biological agents that selectively deliver transgenes to tumor cells and are not permissible in normal cells. The first clinical candidate retroviral replicating vector (RRV) (DB107, vocimagene amiretrorepvec) delivers a

transgene, cytosine deaminase, to convert the non-toxic prodrug 5-fluorocytosine (5-FC) to an intracellular chemotherapeutic, 5-fluorouracil. Recently, phase III randomized clinical trials (Toca 5, NCT02414165) using the first clinical candidate DB107 (formerly named Toca511) demonstrated an improvement in survival in a select

subgroup of patients with a novel biomarker, DGM7 compared to patients receiving standard of care alone (SOC) (18.3 vs. 12.0 months, HR: 0.5, p