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

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be eligible for study entry:

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 HealthOrganization 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 candidatefor >= 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:

9. Platelet count >= 60,000/mm^3

10. Hemoglobin >= 10 g/dL

11. Absolute neutrophil count (ANC) >= 1,500/mm^3

12. Absolute lymphocyte count >= 500/mm^3

13. Total bilirubin <=1.5 x upper limit of normal (ULN) (unless patient hadGilbert's syndrome)

14. alanine aminotransferase (ALT) <= 2.5 x ULN

15. Estimated glomerular filtration rate of at least 50 mL/min by Cockcroft GaultFormula

16. Female participants of child-bearing potential and male participants must agree touse adequate contraception (hormonal or barrier method of birth control; abstinence)for 30-days prior to the first administration of study drug, for the duration ofstudy participation, and for 90-days following completion of the therapy. Should afemale participant become pregnant or suspect a pregnancy while participating inthis study, the treating physician must be informed immediately. IF a maleparticipant impregnates or is suspected of impregnating a woman while participatingin this study, the treating physician must be informed immediately.

• A female of child-bearing potential is any women (regardless of sexualorientation, having undergone a tubal ligation, or remaining celibate by choice) whomeets the following criteria:

• 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 withthe scheduled visits, treatment schedule, laboratory testing and other requirementsof the study.

Exclusion Criteria:

Participants may not meet any of the following exclusion criteria to be eligible for study entry:

1. Prior treatment for High Grade Glioma (HGG).

2. History of other malignancy unless the participant has been disease-free for atleast 5 years. Adequately treated basal cell carcinoma or squamous cell skin canceris not exclusionary regardless of time, as well as localized prostate carcinoma orcervical carcinoma in situ after curative treatment.

3. Histological confirmed oligodendroglioma (IDH-mutant and 1p.19q-codeleted) or mixedglioma.

4. A contrast-enhancing brain tumor that is any of the following:

5. Multi-focal (defined as 2 separate areas of presumed tumor whether contrastenhancing or not, measuring at least 1cm in 2 planes that are not contiguous

6. Associated with either diffuse subependymal or leptomeningeal dissemination or

7. > 5cm in any dimension.

8. Participant has or had an active infection requiring antibiotic, antifungal orantiviral therapy in the 4 weeks preceding study Cycle 1: Day 1.

9. Participant has any bleeding diathesis, or must take anticoagulants, or antiplateletagents, including nonsteroidal anti-inflammatory drugs (NSAIDs), at the time of thescheduled resection that cannot be interrupted for surgery.

10. Participant is HIV positive.

11. 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 andHCV-RNA) or Hepatitis B and C co-infection (positive test for HBsAg or HBcAb andpositive test for HCV Antibody).

12. Participant has a history of allergy or intolerance to flucytosine (DB107-FC).

13. Participant has a gastrointestinal disease that would, in the opinion of theInvestigator, prevent him or her from being able to swallow or absorb flucytosine.

14. Participant intends to undergo treatment with the Gliadel® wafer at the time ofresection surgery or has received Gliadel® wafer < 30 days from Cycle 1: Day 1.

15. Severe pulmonary, cardiac or other systemic disease, which as per Investigatorassessment would prevent surgical resection.

16. Participant who have any other disease or condition, which as per Investigatorassessment may affect the participant's compliance or place the participant athigher risk of potential treatment complications.