Association of Peripheral Blood Immunologic Response to Therapeutic Response to Adjuvant Treatment With Immune Checkpoint Inhibition (ICI) in Patients With Newly Diagnosed Glioblastoma or Gliosarcoma

• INCLUSION CRITERIA:

• Participants must have newly diagnosed histologically confirmed primary glioblastomaor gliosarcoma

• Participants must have undergone an extensive resection of unifocal, confined to thesupratentorial compartment, tumor.

• Participant must have completed chemoradiation (external beam radiation withconcurrent temozolomide) a maximum of 5 weeks prior to initiation of study therapy.Potential participants who have a limited short term, reversable, unrelated to theirunderlying disease, concurrent illness, the initiation of treatment may be delayedup to 14 days, if the participant meet all other I/E criteria at that time.

• Age greater than or equal to 18 years.

• Karnofsky greater than or equal to 70%

• Participants must have adequate organ and marrow function as defined below:

• Absolute neutrophil count greater than or equal to 1,500/mcL

• Platelet Count >100,000/mcL

• Hemoglobin > 9.0 g/dL (may be transfused to achieve this level)

• BUN less than or equal to 30 mg/dL

• Serum creatinine less than or equal to 1.7 mg/dL or creatinine clearance asmeasured by 24 hour urine collection as > 60 ml/min.

• Total bilirubin (except participants with Gilbert s Syndrome, who are eligiblefor the study but exempt from the total bilirubin eligibility criterion) lessthan or equal to 2.0 mg/dL

• ALT and AST less than or equal to 2.5x institutional upper limit of normal.

• The effects of study treatment on the developing human fetus are unknown. For thisreason, participants of reproductive potential must agree to abstinence or useadequate contraception which includes a combination of TWO of the following:

• Barrier method of contraception: condoms (male or female) with or without aspermicidal agent, diaphragm, or cervical cap with spermicide

• IUD

• Hormone-based contraceptive

• Tubal ligation

Note: Consider use in individuals of child-bearing potential (IOCBP) only or both individuals who can father children and IOCBP starting from the enrollment and for the duration of study treatment and up to 6 months (IOCBP) after the last dose of study drug and 6 months (if individual can father children) after the last dose of temozolomide. Should a IOCBP become pregnant or suspect pregnancy while the individual or partner is participating in this study, the individual should inform the treating physician immediately.

-The participant must be able to understand and be willing to sign a written informed consent document.

EXCLUSION CRITERIA:

• Definitive clinical or radiologic evidence of progressive disease.

• Prior placement of Gliadel wafer or local brachytherapy. Note: Tumor Treating Fieldsare allowed.

• Participants who are receiving any other investigational agents.

• Participants who have a history of receiving immune therapy, such as a vaccinetherapy, dendritic cell vaccine or intracavitary or convectional enhanced deliveryof therapy.

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to nivolumab, ipilimumab or temozolomide.

• History of allergic reactions attributed to gadolinium contrast.

• History of severe hypersensitivity reaction to any monoclonal antibody.

• Prior or concurrent malignancy unless its natural history or treatment does not havethe potential to interfere with the safety or efficacy assessment of theinvestigational regimen.

• Participants with active autoimmune disease or history of autoimmune disease thatmight recur, which may affect vital organ function or require immune suppressivetreatment including systemic corticosteroids. These include but are not limited toparticipants with a history of immune related neurologic disease, multiplesclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or CIDP,myasthenia gravis; systemic autoimmune disease such as SLE, connective tissuediseases, scleroderma, inflammatory bowel disease

(IBD), Crohn s, ulcerative colitis, and hepatitis; and participants with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. Such diseases should be excluded because of the risk of recurrence or exacerbation of disease.

Note: Participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Participants with rheumatoid arthritis and other arthropathies, Sjogren s syndrome, psoriasis controlled with topical medication, and participants with positive serology, such as antinuclear antibodies (ANA) and anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.

• The participant must not be currently on a corticosteroid dose greater thanphysiologic replacement dosing defined as 30 mg of cortisone per day or itsequivalent. Participants must have stopped corticosteroids above this threshold atleast 7 days prior to initiation of study treatment.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations (within timeframes identifiedin the bullets below) that

would limit compliance with study requirements.

• Individual who are pregnant are excluded from this study because study treatmentpotential for teratogenic or abortifacient effects is unknown. Because there is anunknown but potential risk for adverse events in nursing infants secondary to studytreatment of the mother, breastfeeding should be discontinued.

• Known active, chronic, or history of hepatitis infection.