Nivolumab and Temozolomide Versus Temozolomide Alone in Newly Diagnosed Elderly Patients With GBM

Inclusion Criteria:

1. Adults, aged greater than or equal to 70 years, or aged 65-69 years if long courseRT is inappropriate, with newly diagnosed histologically confirmed GBM (WHO grade IVglioma including gliosarcoma) following surgery

2. Tissue available for MGMT testing

3. ECOG 0-2

4. Life expectancy of >12 weeks

5. Adequate bone marrow function (platelets > 100 x 10^9/L, ANC > 1.5 x 10^9/L)

6. Adequate liver function (ALT/AST < 1.5 x ULN)

7. Adequate renal function (creatinine clearance > 30 ml/min measured usingCockcroft-Gault

8. Willing and able to comply with all study requirements, including treatment, timingand/or nature of required assessments including MRI

9. Signed, written informed consent

Exclusion Criteria:

1. Specific comorbidities or conditions (e.g. psychiatric) or concomitant medicationswhich may impact with the administration of study related treatments or procedures

2. Other co-morbidities or conditions that may compromise assessment of key outcomes

3. Prior chemotherapy or cranial radiation within the last 5 years. Prior orconcomitant therapies for GBM (except surgery).

4. History of another malignancy within 2 years prior to registration. Patients with apast history of adequately treated carcinoma-in-situ, basal cell carcinoma of theskin, squamous cell carcinoma of the skin, or superficial transitional cellcarcinoma of the bladder are eligible. Patients with a history of other malignanciesare eligible if they have been continuously disease free for at least 2 years afterdefinitive primary treatment.

5. Significant infection, including chronic active hepatitis B, hepatitis C, or HIV.Testing for these is not mandatory unless clinically indicated

6. Active, known or suspected autoimmune disease. Subjects with type I diabetesmellitus, hypothyroidism only requiring hormone replacement, skin disorders (such asvitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions notexpected to recur in the absence of an external trigger are permitted to enroll.

7. For symptoms related to GBM, the need for >4 mg/day of dexamethasone or >20 mg/dayprednisone (or equivalent) at the time of screening.

8. For a condition other than GBM, the need for >2 mg/day of dexamethasone or >10mg/day prednisone (or equivalent) or other immunosuppressive medications within 14days prior to randomisation. Exceptions to this include the use of inhaled ortopical steroids >10 mg/day prednisone (or equivalent), which are permitted in theabsence of active autoimmune disease.