• Arms A \& B: Recurrent high grade glioma (2021 WHO Grades 3 and 4), defined as participants who have progressed on or following standard therapy, which includes maximal surgical resection, temozolomide, and fractionated radiotherapy.

• Arm C, D, \& E: Newly diagnosed glioblastoma (2021 WHO Grade 4), who have not received any tumor directed intervention other than biopsy or resection.

• Candidate for clinical resection of rHGG (Arms A \& B) or nGBM (Arms C \& D).

• Adequate archival or biopsy tissue available for testing of EGFR alterations. The tissue must have evidence of EGFR alterations including variants, fusion, and mutations with or without amplifications. rHGG participants with EGFR fusion will be solely enrolled into Arm B.

• Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.

• Provision of signed and dated, written informed consent (personally or by the legally authorized representative, if applicable) prior to any study specific procedures, sampling and analyses.

• Age ≥ 18 at time of consent

• Have a performance status (PS) of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale.

• Ability to swallow oral medications.

• Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):

‣ Absolute neutrophil count ≥ 1,500/mcL

⁃ Platelets ≥ 100,000/mcL (at time of surgery)

⁃ Hemoglobin ≥ 8.5 g/dL (Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)

⁃ Total bilirubin ≤ 1.5 X ULN (Participants with Gilbert's syndrome with a total bilirubin ≤ 3.0 times ULN and direct bilirubin within normal limits are permitted.)

⁃ AST (SGOT) ≤ 3 X institutional ULN

⁃ ALT (SGPT) ≤ 3 X institutional ULN

⁃ Serum creatinine ≤ 1.5 X ULN or estimated creatinine clearance ≥ 60 mL/min (calculated using Institutional standard method)

• Participants on corticosteroids at baseline must be on stable or decreasing doses for at least 5 days prior to Day 1.

• Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.

• For females of reproductive potential: use of highly effective contraception and agreement to use such a method during study participation until the end of treatment administration and for 16 weeks after the last dose of study drug.

• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner until the end of treatment administration and for 16 weeks after the last dose of study drug.

• Agreement to adhere to Lifestyle Considerations throughout study duration.