2. For both newly diagnosed and recurrent patients, pathologically documented supratentorial WHO grade 4 GBM with a confirmed EGFRvIII mutation at the most recent diagnosis, with radiographic contrast enhancing disease that is ≤ 4 cm in maximal diameter in any plane before resection.

i. ndGBM patients: Must have undergone surgical resection of their tumor. Patients are still eligible if they have measurable or non-measurable residual enhancing tumor following resection, providing they meet all other eligibility criteria. Newly diagnosed patients must complete standard of care RT with or without TMZ before participation, depending on the MGMT promoter methylation status as follows:

1. Patients with methylated MGMT promoter status should have received standard of care concomitant RT and TMZ, followed by 6 cycles of adjuvant TMZ, before they can participate in this study

2. Patients with an unmethylated MGMT promoter status should have received standard of care RT, but need not have received concomitant TMZ or 6 cycles of adjuvant TMZ and can be enrolled after 4 weeks from completion of standard of care RT

3. Patients whose MGMT status is unknown or indeterminate will be treated as though they have a methylated MGMT promotor status for eligibility purposes

4. RT for 3 or 6-week courses are accepted as follows:

* Typically, 59.4-60 Gy over approximately 6 weeks duration, if under 65 years old

* A minimum of 40 Gy over 3 weeks duration, if 65 years or older

5. Patients who progress during RT or within 4 weeks after completion of RT are not eligible.

ii. rGBM patients at first progression: Must have pathological or radiographic confirmation of their tumor recurrence that is ≤ 4 cm in maximal diameter in any plane.

Note: Patients that undergo total gross resection at time of recurrence are eligible to enroll. Patients are still eligible if they have measurable or non-measurable residual enhancing tumor following resection, providing they meet all other eligibility criteria.