Inclusion Criteria:

PRE-REGISTRATION

• Histologically confirmed glioblastoma (World Health Organization [WHO] grade IV) presenting at first or second recurrence including secondary glioblastoma.
• Presence of measurable disease, as defined by a bidimensionally measurable lesion on magnetic resonance imaging (MRI) with a minimum diameter of 10 mm in both dimensions, prior to resection or biopsy of recurrent tumor.
• Tissue available from surgical resection or biopsy of recurrent tumor ≤ 14 days prior to pre-registration, or planned surgery or biopsy of recurrent tumor ≤ 14 days after pre-registration.
• Does not require > 4 mg dexamethasone beyond the perioperative period defined as the time ≤ 2 weeks after surgical procedure.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Able to undergo brain MRI with contrast.
• Absolute neutrophil count ≥ 1500/mm^3.
• Platelet count ≥ 100,000/mm^3.
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN).
• If Gilbert syndrome, then total bilirubin ≤  3 x ULN.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN.
• Creatinine ≤ 1.5 x ULN OR creatinine clearance (CrCl) ≥ 50 mL/min (if using the Cockcroft-Gault formula).

REGISTRATION

• Tissue obtained from biopsy or resection at first or second recurrence exhibits TMB ≥ 20 on FoundationOne CDx testing.

Exclusion Criteria:

• No active autoimmune disease or history of autoimmune disease.
• These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease.
• Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
• Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• No prior treatment with checkpoint blockade therapies (anti-CTLA4, anti-PD1/PD-L1) or bevacizumab.