Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme

Inclusion Criteria

• Signed informed consent.
• Age ≥ 18 years.
• Present with newly diagnosed supratentorial Glioblastoma (GBM) with a tissue diagnosis that has been established following either a surgical resection or biopsy. This includes treatment-naïve -(chemotherapy and radiotherapy)- patients with prior diagnosis of a lower grade astrocytoma that has been upgraded to a histologically verified GBM.
• Karnofsky performance score of 70 or higher.
• Patients entering the study must be on a stable dose of up to 12 mg (maximum) of Dexamethasone (or equivalent) daily for symptoms related to cerebral edema. Following the first dose of avelumab, the duration of treatment with the current dose of dexamethasone (maximum 12 mg/day) or equivalent, should be no more than 7 consecutive days. The investigator(s) should make every effort to taper the dexamethasone as soon as symptom improvement allows to the lowest tolerable dose that controls the CNS symptoms.
• Will be or is undergoing or has received the standard therapy of chemo radiation therapy (60Gy in 30 fractions of 2Gy/day with concurrent temozolomide of 75mg/m2 per day PO) no more than 21 days ago.
• Has not yet begun but will begin standard monthly temozolomide therapy.
• Patient must have at least 1 formalin fixed paraffin embedded tumor tissue block representative of glioblastoma available for biomarker analysis and determination of MGMT status (if not already done). If tumor block is not available or not of adequate quality, sufficient pathology material, representative of glioblastoma, must be available.
• Adequate hematological function defined by absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and ALT levels ≤ 2.5 × ULN for all subjects.
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
• Negative serum pregnancy test at screening for women of childbearing potential.
• Highly effective contraception for both male and female subjects if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 60 days after avelumab treatment.
• International normalized ratio (INR) or PT (secs) and activated partial thromboplastin time (aPTT):
• in the absence of therapeutic intent to anticoagulate the subject: INR≤1.5 or PT ≤1.5 x ULN and aPTT ≤1.5 x ULN
• in the presence of therapeutic intent to anticoagulate the subject: INR or PT and aPTT within therapeutic limits (according to the medical standard in the institution).

NOTE: Use of full-dose anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to randomization.

• Willing and able to comply with the protocol as judged by the Investigator

Exclusion Criteria

• Patients who have evidence of leptomeningeal disease.
• Known significant pulmonary, cardiovascular, hepatic disorders or any other disease that in the opinion of the investigator would be contraindicated to receive anti PD-L1 therapy such as avelumab.
• Prior treatment with bevacizumab or any checkpoint immune blockade thérapies.
• Any other concomitant immunosuppressant other than temozolamide and steroids or any recent (within 3 months) experimental therapy.
• Patients who have finished their radiotherapy course more than 3 weeks prior