1. Ability of the patient or their legally authorized representative to understand and willingness to sign and IRB-approved written informed consent form (ICF).
2. 18 Years of age or older or as permitted by applicable local regulations at the time of providing informed consent.
3. Newly diagnosed histologically confirmed GBM, IDH-WT CNS WHO Grade 4 (Louis et al 2021).
4. EGFR status (see below) in the tumor as determined by a commercially available test or a validated laboratory assay (eg, Clinical Laboratory Improvement Amendments [CLIA] or comparable certification):

a. For Part 1 (Safety Lead-in) ONLY: EGFR alterations.

b. For Part 2 (Randomized, Controlled Trial) ONLY: EGFRvIII.

1. For Part 2 (Randomized, Controlled Trial) ONLY: Unmethylated MGMT promoter tumor status based on a validated assay.
2. No treatment for newly diagnosed GBM other than surgery followed by standard-of-care postoperative radiation (54 to 60 Gy) and TMZ chemotherapy.
3. At least 4 weeks since completion of radiation therapy, with a post-radiation MRI obtained 3 to 5 weeks after radiation showing no progression (Appendix D). Note: If the MRI shows pseudo-progression (Dagher et al 2024), the patient is still eligible to enroll in the study.
4. Must have a Karnofsky Performance Status ≥ 70% (Appendix C).
5. Must have adequate bone marrow or organ function as demonstrated by all the following laboratory values:

a. Estimated (using the Cockcroft-Gault equation) or measured creatinine clearance ≥ 36 mL/min.

b. For Part 1 (Safety Lead-in) ONLY: AST or ALT ≤ 2 × ULN.

For Part 2 (Randomized, Controlled Trial) ONLY: AST or ALT ≤ 3 × ULN.

c. Total bilirubin < 1.5 × ULN (for patients with Gilbert’s syndrome, bilirubin < 3.0 × ULN is allowed).

d. Absolute neutrophil count > 1500 cells/μL, unless previous diagnosis of Duffy-null associated neutrophil count, in which absolute neutrophil count > 1000 cells/uL

e. Hemoglobin > 10 g/dL

Note: RBC transfusion is allowed up to 1 week prior to enrollment ONLY for Part 2 (Randomized, Controlled Trial).

f. Platelet count > 100,000 /μL.

Note: Platelet transfusion is allowed up to 1 week prior to enrollment ONLY for Part 2 (Randomized, Controlled Trial).

g. Must have a QTcF ≤ 470 msecs calculated with Fridericia formula. QTcF may be corrected in case of bundle branch block using a standard method of correction (ie, Bogossian formula [Bogossian et al 2020]).

h. Left ventricular ejection fraction (LVEF) ≥ 50%.

1. For patients on corticosteroids at the time of Screening: able to discontinue steroids or taper steroids. At Randomization the corticosteroid dose must be ≤ 20 mg daily of prednisone or ≤ 3 mg daily of dexamethasone, or its equivalent.
2. Women of child-bearing potential must have documentation of a negative serum pregnancy test (beta-human chorionic gonadotropin [β-hCG]) prior to first dose of study treatment.
3. Women of child-bearing potential and male patients whose sexual partners are women of child-bearing potential, must agree to use a highly effective method of contraception to avoid pregnancy during the study and for ≥ 90 days after the last dose of study drug administration. Male patients must refrain from donating sperm during the treatment period. Refer to Appendix F for further details.

Note: Highly effective birth control includes 1) oral, implantable, or injectable combined hormonal (estrogen- and progesterone-containing) or progesterone-only contraceptive associated with inhibition of ovulation plus an acceptable barrier method; 2) intrauterine device; 3) intrauterine hormone-releasing system; or 4) bilateral tubal occlusion, vasectomized partner, or sexual abstinence.

7.2. Subject

Subjects will be excluded from the study if they meet any of the following cr