Study of Pembrolizumab Plus SurVaxM for Glioblastoma at First Recurrence

Inclusion Criteria

• Histologically confirmed diagnosis of World Health Organization Grade IV glioma (glioblastoma or gliosarcoma)
• Previous first line treatment with at least radiotherapy with or without temozolomide
• Documented first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI) performed within 21 days of randomization per RANO criteria.
• If first recurrence of GBM is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either:

-- Histopathologic confirmation of recurrent tumor, or

-- New enhancement on MRI outside of the radiotherapy treatment field

• Karnofsky performance status of 70 or higher or ECOG 0-2
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study drug.
• Previous treatment with anti PD1 will be allowed only in the exploratory arm
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archive tissue
• Screening/Baseline laboratory values must meet the following criteria (laboratory value):

--Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

---Hematological system:

• Absolute neutrophil count (ANC) ≥1500/uL
• Platelets ≥100 000/µL
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.)

---Renal system:

• Creatinine OR Measured or calculated (Creatinine clearance (CrCl) should be calculated per institutional standard) creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN

---Hepatic system:

• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)

--- Coagulation system:

• International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT): ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Male participants:

--A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.

• Female participants:
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 180 days after the last dose of study treatment.

Exclusion Criteria

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1 (except in the exploratory arm), anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agen