Patients will be treated with ipilimumab 3mg/kg IV infusion on day 1 of a 21 day cycle, for a maximum of 2 cycles, followed by standard of care treatment which consists of debulking surgery, radiotherapy and chemotherapy.

Inclusion criteria

1. Histologically confirmed, newly diagnosed de-novo supratentorial glioblastoma (including gliosarcoma)

2. Age 18 years or older

3. Tumour deemed appropriate for surgical debulking

4. ECOG PS 0-1

5. Clinically fit for, and appropriate to receive, neoadjuvant ipilimumab followed by standard of care treatment, based on investigator and MDT judgement

6. Adequate organ and bone marrow function:

• Hb >9 g/dL
• Neutrophils >1.0 x 10⁹/L
• Platelets >100 x 10⁹/L
• Lymphocyte count >1.0 x 10⁹/L

7. Adequate renal function:

• Creatinine clearance of >50mL/min calculated by Cockroft-Gault equation

8. Adequate liver function:

• Bilirubin ≤1.5 x ULN (except for patients with known Gilbert's Syndrome who may have total bilirubin ≤3 x ULN)
• Aspartate or alanine transferase (AST or ALT) ≤2.5 xULN

9. Life expectancy of greater than 12 weeks

10. Willing to comply with the contraceptive requirements of the trial

11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

12. Willing to donate tumour material and serial blood samples

13. Written informed consent

Exclusion criteria

1. Diagnosis of multifocal glioblastoma (multicentric glioblastoma permitted)

2. Prior resecton of glioblastoma leaving inadequate tissue for post investigational treatment resection

3. Secondary glioblastoma (i.e. previous histological or radiological diagnosis of lower grade glioma)

4. Known extracranial metastatic or leptomeningeal disease

5. Prior treatment for glioblastoma other than a limited resection of biopsy

6. Dexamethasone dose >3mg daily (or equivalent) at the time of starting study treatment

7. Antibiotics received within 30 days prior to starting study treatment

8. Intratumoural or peritumoural haemorrhage deemed significant by the treating clinician

9. Active autoimmune disease apart from:

• Skin conditions such as psoriasis, vitiligo or alopecia not requiring systemic treatment
• Type 1 diabetes of thryoid disease, controlled on medication

10. Any evidence of severe or uncontrolled disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)

11. Known hypersensitivity to ipilimumab or any of its excipients

12. Past medical history of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced interstitial disease which required steroid treatment or any evidence of clinically active interstitial lung disease

13. Any condition requiring systemic treatment with corticosteroids (>10 mg prednisolone daily or equivalent) or other immunosuppressive medications within 14 days prior to starting study treatment.  Inhaled or topical steroids, and adrenal replacement steroid doses >10mg daily prednisolone or equivalent are permitted in the absence of active autoimmune disease)

14. Treatment with any other investigational agent within 28 days prior to starting study treatment

15. History of previous cancer within 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and non-melanoma skin lesions

16. Positive serology for Hepatitis B defined as a positive test for HepB surface antigen (HBsAg)

17. Positive serology for Hepatitis C defined as a positive test for HCV antibody

18. Diagnosis of prior immunodeficiency or organ-transplant requiring immunosuppressive therapy or known HIV or acquired immunodeficiency syndrome (AIDS-related illness)

19. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

20. Women who are pregnant or breast feeding