DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma

Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of DB107-RRV administered intracranially followed by intravenous (IV) DB107-RRV and DB107-FC (Phase I).

II. To determine the median progression-free survival (PFS) (informed by biomarker status, DGM7 and patient subsets to minimally include genomic profile and histology) of newly diagnosed HGG patients treated with DB107-RRV combined with DB107-FC delivered with standard of care following tumor resection (Phase IIa).

SECONDARY OBJECTIVES:

I. To confirm the recommended Phase 2 Dose (RP2D) of DB107-RRV and DB107-FC when administered to newly diagnosed HGG patients (Phase I).

II. To evaluate radiographic response by Immunotherapy response assessment in neuro-oncology (iRANO) (Phase I).

III. To assess best overall response rates (complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD)) and overall response rate (CR and PR) of each arm and subset (Phase IIa).

IV. To assess the duration of response of each arm and subset (Phase IIa). V. To assess the median overall PFS and PFS at month 6 (PFS-6) for each arm and subset (Phase IIa).

VI. To assess the median overall survival of each arm and subset (Phase IIa). VII. To evaluate the safety of DB107-RRV administered intracranially followed by IV DB107-RRV and DB107-FC (Phase IIa).

OUTLINE:

Participants will initially be enrolled in Phase I and treated with DB107-RRV intracranially, at time of surgical resection, and intravenously within 8 hours following surgery. Pathology will be performed locally as per standard practice to confirm participant’s HGG diagnosis and Isocitrate dehydrogenase 1 (IDH1) mutation status. Participants in Phase I will then be assigned to one of 2 cohorts: No MGMT methylation (MGMT unmethylated) which will receive DB107-FC and RT following DB107-RRV or Low-High MGMT methylated which will receive DB107-FC, Temozolomide (TMZ) and RT following DB107-RRV. The safety and tolerability will be examined for the Phase I participants and RP2D dose confirmed. New participants will then be enrolled in Phase IIa under the established RP2D determined in Phase I, with the first 2 participants receiving a safety run-in at the RP2D. Once participant safety and tolerability are confirmed, additional participants will be enrolled in the Phase IIa portion of the study. All participants who receive DB107-RRV and DB107-FC will be followed for up to15 years.