Inclusion Criteria:

Cohort A:

1. Subjects with newly diagnosed, untreated, unmethylated MGMT GBM who are eligible for
standard radiation therapy.

Cohorts B, B2, B3 and C:

2. First or second recurrence of GBM by diagnostic biopsy or contrast enhanced MRI per
modified RANO criteria (122), with last baseline MRI confirmation within 14 days
prior to Study Day 1.

NOTE: Recurrence is defined as progression following therapy (i.e., chemotherapy;
radiation). If the subject had a surgical resection for relapsed disease and no
anti-tumor therapy was administered for up to 12 weeks, and the subject has further
evidence of tumor growth or undergoes another resection, this will be considered as
one episode of recurrence.

3. On Study Day 1, at least 12 weeks from prior radiotherapy (unless progressive disease
outside of the radiation field or histopathologic confirmation of unequivocal tumor).

4. Cohort B, B2, B3: No prior VEGF/VEGFR targeted therapy; Cohort C: No more than one
prior bevacizumab regimen.

5. Recovery from any prior treatment clinically significant, related adverse events to
grade 1 or pretreatment baseline with the exception of alopecia and laboratory
values listed per inclusion criteria.

Cohorts A, B, B2, B3 and C:

6. Subjects with measurable or non-measurable disease.

7. Histopathologic confirmation of glioblastoma.

8. At the time of Study Day 1, subjects must be at least 4 weeks since major surgical
procedure, open biopsy, or significant traumatic injury; there should be no
anticipation of need for major surgical procedure during the course of the study.

There should be no core biopsy or other minor surgical procedure, excluding placement
of a vascular access device, within 7 days prior to Study Day 1.

9. Subjects who have previously been treated with the Optune device are eligible for the
study as long as toxicity related to the treatment has resolved to Grade 1 or
baseline.

10. ECOG 1 or Karnofsky performance status of 70.

11. Adequate hematologic, renal and hepatic function, as defined below:

- Absolute Neutrophil Count 1000/mm3

- Platelet count 100,000/mm3

- Total bilirubin 1.5 x ULN; or if subject has Gilbert syndrome, then total
bilirubin 3 x ULN

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 2.0 x ULN

- Creatinine 1.5x ULN or creatinine clearance (CrCl) 50 mL/min (using the
Cockcroft-Gault formula):

- Female CrCl = (140 - age in years) x weight in kg x 0.85 /72 x serum
creatinine in mg/dL

- Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum
creatinine in mg/dL Cohorts B2, B3 and C

- Urinary protein quantitative value of 30 mg/dL in urinalysis or 1+ on
dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample.

12. Age must be greater than or equal to 18 years at date of consent.

13. Written informed consent and any locally required authorization (e.g., Health
Insurance Portability and Accountability Act [HIPAA] in the USA) obtained from the
subject/legal representative prior to performing any protocol-related procedures,
including screening evaluations.

Exclusion Criteria:

All Cohorts

1. Primary tumors localized to the brainstem or spinal cord.

2. Locally directed therapies including but not limited to stereotactic radiosurgery,
re-irradiation, Gliadel, and therapeutics administered by direct injection or
convection-enhanced delivery within 6 months of start of study treatment.

3. Prior exposure to MEDI4736 or other anti-PD-1, anti-PD-L1, anti-CTLA4 antibodies.

4. Presence of diffuse leptomeningeal disease or extracranial disease.

5. Active, suspected or prior documented autoimmune disease (including inflammatory
bowel disease, celiac disease, irritable bowel syndrome, Wegner's granulomatosis and
Hashimoto's thyroiditis). Subjects with vitiligo, type I diabetes mellitus, residual
hypothyroidism due to autoimmune condition only requiring hormone replacement,
psoriasis not requiring systemic treatment, or conditions not expected to recur in
the absence of an external trigger are permitted to enroll.

6. Known primary immunodeficiency or active HIV.

7. Known active or chronic viral hepatitis or history of any type of hepatitis within
the last 6 months indicated by positive test for hepatitis B surface antigen (HBV
sAG) or hepatitis C virus ribonucleic acid (HCV antibody).

8. History of organ transplant requiring use of immunosuppressive medication.

9. History of active tuberculosis.

10. Significant active systemic illness including infections requiring intravenous
antibiotics.

11. Current pneumonitis or interstitial lung disease.

12. Other invasive malignancy within 2 years prior to entry into the study, except for
those treated with surgical therapy only.

13. History of severe allergic reactions to any unknown allergens or any components of
the study drugs.

14. Any prior Grade 3 immune-related adverse event (irAE) or any prior
corticosteroid-refractory irAE.

15. Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study.

16. Lack of availability for follow-up assessments.

17. Lack of availability for Post Study Follow-up contacts to determine relapse and
survival.

18. Women who are breast-feeding or pregnant as evidenced by positive serum pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG).

19. Women of childbearing potential not using a medically acceptable means of
contraception for the duration of the study and unsterilized males not willing to
abide by requirements for contraception as stated in Section 5.4.

20. If a subject previously received another investigational treatment, the last dose of
investigational treatment was administered within 4 weeks of Day 1 of the study.

21. Any condition that, in the clinical judgment of the treating physician, is likely to
prevent the subject from complying with any aspect of the protocol or that may put
the subject at unacceptable risk.

22. Cohorts B2, B3 and C:

- Evidence of hemorrhage on the baseline MRI or CT scan other than those that are
grade 1 and either post-operative or stable on at least two consecutive scans

- Current use of warfarin sodium or any other Coumadin-derivative anticoagulant.
Participant must be off Coumadin-derivative anticoagulants for at least seven
days prior to starting study drug. Low molecular weight heparin and Factor Xa
antagonists are allowed

- History of clinically significant bleeding within 6 months of enrollment

- History of arterial thromboembolism within 12 months prior to enrollment

- Inadequately controlled hypertension (defined as systolic blood pressure 150
and/or diastolic blood pressure > 90 mmHg on antihypertensive medications)

- Any prior history of hypertensive crisis or hypertensive encephalopathy

- Clinically significant cardiovascular disease within 12 months prior to
enrollment (or randomization), including myocardial infarction, unstable angina,
grade 2 or greater peripheral vascular disease, cerebrovascular accident,
transient ischemic attack, congestive heart failure, or arrhythmias not
controlled by outpatient medication, percutaneous transluminal coronary
angioplasty/stent

- Evidence of bleeding diathesis or coagulopathy

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal
abscess within 6 months prior to study enrollment

- Serious, non healing wound, ulcer, or bone fracture

Minimum Eligible Age: 18 Years

Maximum Eligible Age: N/A

Eligible Gender: Both