• Patients must be 18 years of age or older at the time of consent signing.

• Patients must have histologically proven WHO grade IV glioblastoma gliosarcoma which is progressive or recurrent following radiation therapy ± chemotherapy. Glioblastoma is defined using the WHO 2021 criteria and include the diagnosis of molecular GBM

• Patients must be IDH wild type by CLIA-certified laboratory assay available at time of consent.

• Patients must have evidence of EGFR gene amplification by CLIA-certified laboratory assay at time of consent.

• Patients must have measurable disease as per RANO criteria pre-operatively (there is no requirement for post-operative disease to be present or absent). \[cohort A/B only\]

• Patients must be able to tolerate MRIs

• Patients may have no more than 2 prior therapy regimens. \[cohort A/B only\]

• Patients must have recovered from severe toxicity of prior therapy. The following intervals from previous treatments are required to be eligible:

∙ 12 weeks from the completion of radiation

‣ 6 weeks from a nitrosourea chemotherapy

‣ 3 weeks from a non-nitrosourea chemotherapy

‣ 4 weeks from any investigational (not FDA-approved) agents

‣ 6 months from the last treatment with bevacizumab

‣ 2 weeks or 5 half-lives from administration of a non-cytotoxic, FDA-approved agent other than bevacizumab, whichever is longer

• Patients must be undergoing surgery that is clinically indicated as determined by their care providers. \[cohort A/B only\] Patients must be eligible for surgical resection according to the following criteria:

• a. Expectation that the surgeon is able to resect at least 500 mg of tumor from enhancing tumor with low risk of inducing neurological injury.

• Paraffin embedded tissue must be available from initial surgical resection at diagnosis (prior to any treatment). The following amount of tissue is requested: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE unstained slides (5µm thick).

• Patients must have a Karnofsky Performance Status (KPS) ≥60% (i.e. the patient must be able to care for himself/herself with occasional help from others).

• Patients must have the following organ and marrow function:

∙ Absolute neutrophil count \>1,200/mcL

‣ Platelets \>100,000/mcL

‣ Hemoglobin \> 9 g/dL .

‣ Total bilirubin ≤ institutional upper limit of normal, or ≤ 3.0 mg/dL for subjects with Gilbert's syndrome

‣ AST (SGOT) and ALT (SGPT) ≤ 3 × institutional upper limit of normal

‣ Creatinine ≤ institutional upper limit of normal OR Creatinine clearance \>60 ml/min/1.73m2 for patients with creatinine levels above institutional normal

‣ APTT/PTT ≤ 1.5 x institutional upper limit of normal

• Echocardiogram with ejection fraction ≥ 50% and no other clinically significant finding that, in the opinion of the investigator, would increase the subject's susceptibility to cardiac toxicity.

• a. If ECHO cannot be performed for structural or safety reasons, a MUGA may be obtained instead after discussion with treating investigator.

• Patients must have a 12-lead electrocardiogram performed within 2 weeks of treatment start with QT interval corrected for heart rate (QTc) \< 450 msec (using Fridericia's correction), and no clinically significant abnormalities.

• Women of childbearing potential must have a negative serum pregnancy test prior to study entry. Women of childbearing potential and men treated or enrolled on this protocol must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of treatment administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• A negative serum pregnancy test for all female subjects (except postmenopausal) at the screening visit and a negative urine pregnancy test for all female subjects (except postmenopausal) at baseline before the first dose of study drug.

• If female, subject must be either postmenopausal, OR permanently surgically sterile OR, for women of childbearing potential, practicing at least 1 protocol-specified method of birth control that is effective from study Day 1 through at least 4 months after the last dose of study drug.

• If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree from study Day 1 through 4 months after the last dose of study drug to practice the protocol-specified contraception.

• If female, subject must not be pregnant, breastfeeding, or considering becoming pregnant during the study while receiving study drug and for at least 4 months after the last dose of study drug.

• If male, subject must not be considering fathering a child or donating sperm during the study or for 4 months after the last dose of study drug.

• No known active viral hepatitis infection (including hepatitis B and C) or human immunodeficiency virus (HIV) with the following exceptions:

‣ Subjects with a history of hepatitis B that is considered cured may be enrolled at the discretion of the treating investigator.

⁃ Subjects with a history of hepatitis C that is considered cured with definitive therapy may be enrolled at the discretion of the treating investigator.

⁃ Subjects with HIV and undetectable viral load, so long as ongoing antiretroviral therapy does not pose risk of adverse drug-drug interactions, at the discretion of the treating investigator.

• Patients must have no concurrent malignancy that requires active therapy.

• Patients must be able to swallow medication by mouth, either tablets or dispersed in solution.