Synergism of dendritic cell vaccination and anti-PD-L1 immune check-point blockade to sensitize recurrent glioblastoma to anti-tumoral immunity

Prior treatment

• Treatment with live, attenuated vaccine within the last four weeks.
• Treatment with specific immunostimulatory agents within the last six weeks or five half-lives of the drug (whichever is longer).
• Evidence for any active infection requiring hospitalization or i.v. antibiotics or anti-viral treatment within two weeks prior to trial enrollment.
• Evidence for any active infection requiring hospitalization or i.v. antibiotics or anti-viral treatment within two weeks prior to trial enrollment.

Other illness

• Severe acute or chronic medical conditions that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the opinion of the Investigator, would make the patient inappropriate for entry into the trial. This includes, but is not limited to the following: o Immunosuppressive disease / immunodeficiency o Chronic renal disease / failure o Cardiovascular: uncontrolled hypertension, unstable angina, myocardial infarction or symptomatic congestive heart failure within the past 12 months or serious uncontrolled cardiac arrhythmia o Severe poorly controlled diabetes o Planned other major surgery.
• History of pneumonitis.
• Medical history of severe autoimmune disorder or patients with organ allograft.
• Medical history of bleeding diathesis or coagulopathy.
• Known allergy or intolerability to any component of the GlioVax DC vaccine or Atezolizumab.
• Infection with HIV, HBV, HCV, HEV, Parvo B19 Virus, Treponema pallidum or others as required by national law.

Lab values

• Prior malignancy during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with Prostate-Specific Antigen (PSA) level less than ULN.

Other

• Preexisting severe myelosuppression.
• Known pregnancy or breast feeding.

• Patients 18 - 75 years of age at re-resection.
• Adequate hepatic (serum glutamate pyruvate transferase/alanine transaminase (SGPT/ALT), serum glutamic oxaloacetate transaminase/aspartate transaminase (SGOT/AST) and alkaline phosphatase (ALP) ≤ 3-times upper limit of normal (ULN); bilirubin ≤ 1.5-times ULN) and renal functions (creatinine ≤ 1.5-times ULN).
• Adequate bone marrow function (hemoglobin ≥ 10 g/dl, thrombocytes ≥ 100,000/μl, white blood cell count ≥ 3,000/μl; neutrophil count ≥ 1,500/μl).
• Quick value with international normalized ratio (INR) (in absence of anticoagulation treatment) ≤ 1.5.
• GBM (IDHwildtype, WHO grade 4) at 1st recurrence (neuropathological confirmation after surgery).
• Standard radiochemotherapy and at least three cycles of adjuvant TMZ chemotherapy completed.
• Primary tumor tissue and initial MRI scans available for analyses.
• Adequate venous access for leukapheresis (both arms).
• Near-complete resection (≤ 5 ml residual contrast enhancing tumor volume) after fluorescence-guided surgery, confirmed by neuroradiologist on MRI scan within 72 h postoperative; second look surgery is possible, if medically indicated.
• Karnofsky performance status (KPS) ≥ 70%.
• Successful production of sterile, avital tumor lysate (≥ 60% tumor cell content, 3.5 mg protein).
• Systemic corticosteroids ≤ 2 mg of dexamethasone or equivalent per day at baseline (use of corticosteroids during the treatment period should be avoided, however it is possible if clinically indicated).