Azeliragon and Chemoradiotherapy in Newly Diagnosed Glioblastoma

Inclusion Criteria:

1. Patient must have histologically confirmed newly diagnosed glioblastoma (GBM, worldhealth organization (WHO) grade IV). The histological diagnosis must have been madeafter biopsy or neurosurgical tumor resection. Note: Patients should be isocitrate dehydrogenase (IDH) wild type diagnosed locally

2. The local O-6-Methylguanine-DNA Methyltransferase (MGMT) report determination shouldbe available and should be uploaded to the electronic case report form (eCRF).

3. Patient should have had a gross total or subtotal resection performed < 7 weeksprior to enrollment, documented at postoperative MRI. Patients who have had a biopsyonly without resection are not eligible.

4. Patient deemed suitable by the treating physician to receive the standardradiotherapy regimen in combination with temozolomide.

5. Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 70 years of age.

6. Patient may have received and continue to receive corticosteroids, but must be on astable or decreasing dose for at least 14 days prior to first dose of studytreatment.

7. Patient has not received prior chemotherapy or radiotherapy.

8. Patient has adequate biological parameters as demonstrated by the following bloodcounts at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0:Absolute neutrophil count (ANC) ≥ 1.0 × 109/L; Platelet count ≥ 75,000/mm3 (75 × 109/L); Hemoglobin (Hgb) ≥ 9 g/dL without transfusion or growth factor support

9. Patient has the following blood chemistry levels at Screening (obtained ≤ 14 daysprior to enrollment) and at Baseline-Day 0:

10. aspartate amino-transferase (AST)(SGOT), alanine transferase (ALT)(SGPT) ≤ 2.5 × upper limit of normal range (ULN). Total bilirubin ≤ 1.5 × ULN.

11. Estimated creatinine clearance of > 60 mL/min (per Cockcroft -Gault formula)

12. Patients with a QTC of ≤ 480 msec

13. Patient has ECOG performance status of ≤ 2

14. Patient has been informed about the nature of the study, and has agreed toparticipate in the study, and signed the Informed Consent Form (ICF) prior toparticipation in any study-related activities.

Exclusion Criteria:

1. Patients with a history of other malignancies, except: adequately treatednon-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or othersolid tumors curatively treated with no evidence of disease for > 5 years

2. Patients with a serious active infection (such as a wound infection requiringparenteral antibiotics) at the time of inclusion or other serious underlying medicalconditions that would impair the ability of the patient to receive protocoltreatment

3. Patients with any condition (e.g. psychological, geographical, etc.) that does notpermit compliance with the protocol.

4. Patients who have had treatment with any investigational cancer drug prior to thefirst dose of study treatment.

5. Patient has experienced an increase of ECOG to > 2 between Screening and the time offirst dose with azeliragon.

6. Patients receiving CYP2C8 inhibitors

7. Patient is unwilling or unable to comply with study procedures, including, but notlimited to self-administration of oral medication.

8. Patients with a gastrointestinal condition that could interfere with swallowing orabsorption.

9. Females of childbearing potential who are sexually active or males with femalepartners of childbearing potential, where either the female or the male is unwillingto use a highly effective method of contraception during the trial and for 6 monthsafter the last administration of azeliragon.

10. Patients with concurrent participation in another interventional clinical trial oruse of another investigational agent within 14 days of starting azeliragon. Patientswho are participating in non-interventional clinical trials (e.g., QOL, imaging,observational, follow-up studies, etc.) are eligible, regardless of the timing ofparticipation.