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

Eligibility Criteria

• 1. Participant has provided written informed consent.
• 2. Participant is between 18 years of age and 75 years of age, inclusive.
• 3. Participant must have a Karnofsky Performance Scale (KPS) of \>= 70.
• 4. Participant must have newly diagnosed adult-type diffuse gliomas (World Health Organization Classification 2021) that has not been previously treated with surgery, radiation or chemotherapy (specifically astrocytoma, Isocitrate dehydrogenase (IDH)-mutant or glioblastoma, IDH-wildtype).
• 5. Based on the pre-operative evaluation by neurosurgeon, participant is a candidate for \>= 80% resection of the enhancing region.
• 6. The primary tumor must be made available for central testing for IDH1 mutation, O6-methylguanine-DNA methyl-transferase (MGMT) methylation status.
• 7. Willing to provide a blood sample to determine Denovo Genomic Marker 7 (DGM7) status.
• 8. Laboratory values adequate for patient to undergo surgery, including:
• 1. Platelet count \>= 60,000/mm\^3
• 2. Hemoglobin \>= 10 g/dL
• 3. Absolute neutrophil count (ANC) \>= 1,500/mm\^3
• 4. Absolute lymphocyte count \>= 500/mm\^3
• 5. Total bilirubin \<=1.5 x upper limit of normal (ULN) (unless patient had Gilbert's syndrome)
• 6. alanine aminotransferase (ALT) \<= 2.5 x ULN
• 7. Estimated glomerular filtration rate of at least 50 mL/min by Cockcroft Gault Formula
• 9. Female participants of child-bearing potential and male participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for 30-days prior to the first administration of study drug, for the duration of study participation, and for 90-days following completion of the therapy. Should a female participant become pregnant or suspect a pregnancy while participating in this study, the treating physician must be informed immediately. IF a male participant impregnates or is suspected of impregnating a woman while participating in this study, the treating physician must be informed immediately.
• * Has not undergone a hysterectomy or bilateral oophorectomy or
• * Has not had \>= 12 months of non-therapy-induced amenorrhea.
• 10. Participants must not be breastfeeding.
• 11. Participants must have the ability to understand, and the willingness to comply with the scheduled visits, treatment schedule, laboratory testing and other requirements of the study.
• 1. Prior treatment for High Grade Glioma (HGG).
• 2. History of other malignancy unless the participant has been disease-free for at least 5 years. Adequately treated basal cell carcinoma or squamous cell skin cancer is not exclusionary regardless of time, as well as localized prostate carcinoma or cervical carcinoma in situ after curative treatment.
• 3. Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixed glioma.
• 4. A contrast-enhancing brain tumor that is any of the following:
• 1. Multi-focal (defined as 2 separate areas of presumed tumor whether contrast enhancing or not, measuring at least 1cm in 2 planes that are not contiguous
• 2. Associated with either diffuse subependymal or leptomeningeal dissemination or
• 3. \> 5cm in any dimension.
• 5. Participant has or had an active infection requiring antibiotic, antifungal or antiviral therapy in the 4 weeks preceding study Cycle 1: Day 1.
• 6. Participant has any bleeding diathesis, or must take anticoagulants, or antiplatelet agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of the scheduled resection that cannot be interrupted for surgery.
• 7. Participant is HIV positive.
• 8. Participant has Hepatitis B (positive test for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and positive test for hepatitis B Virus (HBV) DNA) or Hepatitis C (positive tests for hepatitis C Virus (HCV) Antibody and HCV-RNA) or Hepatitis B and C co-infection (positive test for HBsAg or HBcAb and positive test for HCV Antibody).
• 9. Participant has a history of allergy or intolerance to flucytosine (DB107-FC).
• 10. Participant has a gastrointestinal disease that would, in the opinion of the Investigator, prevent him or her from being able to swallow or absorb flucytosine.
• 11. Participant intends to undergo treatment with the Gliadel® wafer at the time of resection surgery or has received Gliadel® wafer \< 30 days from Cycle 1: Day 1.
• 12. Severe pulmonary, cardiac or other systemic disease, which as per Investigator assessment would prevent surgical resection.
• 13. Participant who have any other disease or condition, which as per Investigator assessment may affect the participant's compliance or place the participant at higher risk of potential treatment complications.