DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma
NCT Number: NCT06504381
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: High Grade Glioma|MGMT-Unmethylated Glioblastoma|MGMT-Methylated Glioblastoma
Interventions: GENETIC: DB107-RRV|GENETIC: DB107-FC|RADIATION: Radiation Therapy (RT)|DRUG: Temozolomide|PROCEDURE: Magnetic Resonance Imaging (MRI)|PROCEDURE: Surgical resection
Sponsor: Nicholas Butowski
Collaborators: California Institute for Regenerative Medicine (CIRM)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 70
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2039-11-30
Locations: University of California, San Francisco, California, 94143, United States

Summary:
This is a multicenter, open-label study of DB107-RRV (formerly Toca 511) and DB107-FC (formerly Toca FC) when administered following surgical resection in newly diagnosed High Grade Glioma (HGG) patients. The study is designed to evaluate whether treatment with DB107-RRV in combination with DB107-FC when added to standard of care provides clinical benefit to newly diagnosed HGG when compared to historical performance previously determined in well controlled clinical trials published in the peer reviewed literature. This study is going to be conducted in newly diagnosed HGG patients receiving with maximum surgical resection treatment followed by radiation and temozolomide treatment using the established Stupp Protocol for O6-methylguanine-DNA methyl-transferase (MGMT) methylated patients or radiation therapy for MGMT unmethylated patients.

Primary Outcome Measures: Proportion of participants with dose limiting toxicities (Phase I), Tolerability is defined as the proportion of participants receiving at least one dose of DB107-RRV and DB107-FC with a reported dose-limiting toxicity for all participants in Phase I., Up to 1 year|Proportion of participants with treatment-emergent adverse events (Phase I), Safety is defined as the proportion of participants with treatment-emergent adverse events as classified by the Medical Dictionary for Regulatory Activities (MEDDRA) preferred terms and graded for severity according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for participants in Phase 1., Up to 15 years|Median Progression free survival (PFS) by biomarker status (Phase IIa), PFS is defined as time from first receipt of DB107-RRV until progression or death, whichever occurs first for newly diagnosed HGG patients with unmethylated MGMT and methylated MGMT. Participants without an event will be censored at the last disease assessment. PFS (months) = (earlier date of documentation of progression of disease or death/censored - date of first dose of DB107-RRV+1) (365.25/12) using Immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria to determine disease status. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method., Up to 15 years
Secondary Outcome Measures: Recommended Phase 2 Dose (RP2D) (Phase I), The confirmed RP2D of DB107-RRV and DB107-FC implemented for participants enrolled in Phase IIa will be reported., Up to 5 years|Overall Response Rate (ORR) (Phase IIa), ORR is defined as the percentage of subjects who obtained either a disease status of CR or PR according to iRANO criteria per investigator., Up to 15 years|Median Progression-free survival (PFS) at 6 months (Phase IIa), PFS is defined as time from first receipt of DB107-RRV until progression or death, whichever occurs first at the 6-month visit. Participants without an event will be censored at the last disease assessment. PFS (months) = (earlier date of documentation of progression of disease or death/censored - date of first dose of DB107-RRV+1) (365.25/12) using Immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria to determine disease status. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method., Up to 6 months|Median Progression-free survival (PFS) (Phase IIa), PFS is defined as time from first receipt of DB107-RRV until progression or death, whichever occurs first at the 6-month visit. Participants without an event will be censored at the last disease assessment. PFS (months) = (earlier date of documentation of progression of disease or death/censored - date of first dose of DB107-RRV+1) (365.25/12) using Immunotherapy Response Assessment for Neuro-Oncology (iRANO) criteria to determine disease status. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method., Up to 15 years|Median Overall Survival (OS) at 6 months (Phase IIa), Overall survival at 6 months is defined as the time from the date of first DB107-RRV injection until death. Participants who are alive at 6 months will be censored. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method., 6 months|Median Overall Survival (OS) (Phase IIa), Overall survival will be analyzed using the date of first DB107-RRV injection as baseline until death, participant withdrawal, or study closure. The median and the 95% confidence interval will be estimated using the Kaplan-Meier method., Up to 15 years