TIP-08. Trial in progress update: A phase 1/2 study of intracranial and intravenous multi-dosing of DB107-RRV (formerly Toca 511) and DB107-FC (5-fluorocytosine) in combination with radiation ± temozolomide (TMZ) in patients with newly diagnosed high

Abstract BACKGROUND DB-107 RRV, a retroviral replicating vector, delivers a cytosine deaminase gene (yCD2) to tumor cells. This enzyme converts DB107-FC into chemotherapeutic agent 5-fluorouracil (5-FU), inducing tumor cell apoptosis. While prior studies targeted recurrent high-grade glioma (HGG) patients with DB107-RRV as monotherapy or with standard of care (SOC), via intracranial (IC) or intravenous (IV) dosing, this is the first study utilizing the neoadjuvant combination of DB107-RRV and DB107-FC in newly diagnosed HGGs. This Phase 1/2 study evaluates safety and efficacy of local and systemic multi-dosing of DB-107 RRV and DB107-FC with SOC radiation ± TMZ based on MGMT methylation incorporating DGM7+ biomarker analysis to investigate its role in improving outcomes. METHODS A multi-center, open-label, Phase 1/2 trial enrolling patients with suspected newly diagnosed HGGs into two SOC treatment arms. Following surgical confirmation, patients receive 40 IC injections of DB107-RRV (4.0 x 108 TU) into the resection cavity and a single IV infusion of DB107-RRV (1.4 x 109TU) following tumor resection. MGMT methylated (mMGMT) patients receive radiotherapy and TMZ with DB107-FC, while MGMT unmethylated (uMGMT) patients receive SOC radiotherapy and DB107-FC. After radiation, patients receive IV DB107-RRV on Day 7 and 14, followed by six cycles of adjuvant therapy (DB107-FC + TMZ for mMGMT; DB107-FC for uMGMT). The Phase 1 primary objective is evaluating safety and tolerability of DB107-RRV’s dual-route administration. The Phase 2 primary objective is determining median progression free survival correlated to DGM7+/- status, viral DNA in blood, and adverse events. RESULTS The study is currently enrolling. To date, DB107-RRV multimodal delivery has completed for five patients with histopathologic glioblastoma confirmation, without delays in surgical care. Two mMGMT patients are entering adjuvant therapy, one mMGMT patient is beginning radio/chemotherapy + DB107-FC, and two patients are awaiting MGMT results. No significant toxicity related to study drug has been observed.