Pilot Study of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency

Inclusion Criteria: 1. Patient previously diagnosed with WHO grade 4 IDH-wildtype GBM, determined through genomic and/or histopathological analysis. 2. Prior treatment for GBM with surgical resection and standard of care TMZ and radiation therapy. 3. Patient who has undergone repeat surgery (including biopsy or resection) for rGBM. 4. MMR deficiencies confirmed per standard of care immunohistochemical analysis or Next Generation Sequencing (NGS) of the patient's surgical sample from the time of initial GBM diagnosis or recurrence. 5. Area of sonication using the NaviFUS platform is \>30 mm from the skull surface, assessed on the Investigator's review of the screening MRI. 6. Age ≥18 years. 7. Karnofsky Performance Scale (KPS) \>70. 8. Adequate organ and marrow function: Leukocytes ≥2,500/mm3 Absolute Neutrophil Count ≥1,500/mm3 Absolute Lymphocyte Count ≥800/mm3 Platelets ≥100,000/mm3 Hemoglobin ≥8 g/dL 9. Negative serum or urine pregnancy test in a female patient of childbearing potential. 10. Patient or a legally-authorized representative must provide study-specific informed consent. Exclusion Criteria: 1. Multifocal or leptomeningeal disease observed at the time of GBM recurrence. 2. Patient for whom the repeat surgical cavity is ≤30 mm from the skull surface or otherwise not reasonably accessible for sonification using the NaviFUS platform, assessed on screening MRI. 3. Patient with a prior or concurrent malignancy that is deemed to be clinically significant in the context of rGBM. 4. Patient receiving concurrent treatment with an immune checkpoint inhibitor, other investigational agent, or live vaccine administered within 14 days prior to the first dose of trial treatment. 5. Prior treatment with an immune checkpoint inhibitor agent. 6. Period of less than 28 days from the time of the patient's receipt of other systemic anti-cancer therapies to the proposed date of first trial treatment. 7. Treatment with systemic corticosteroids at an increased dose or dose of ≥10 mg of prednisone (or equivalent) daily within the 5 days prior to starting trial treatment, or treatment with systemic corticosteroids for other indications. 8. Patient with a history of organ transplant or autoimmune disorder requiring active immunosuppression. 9. Patient with current recreational drug use or a history of substance use disorder. 10. Patient with an active concurrent comorbidity that, in the opinion of the Investigator, would pose a safety concern for the patient's participation in this clinical trial.