GI-102 Alone or With Pembrolizumab Before Surgery for Treatment of Recurrent or Progressive IDH Wildtype Glioblastoma and IDH Mutated Grade 4 Astrocytoma

Exclusion Criteria34

• Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential or able to father a child who are unwilling to employ adequate contraception
• Signs or symptoms of life-threatening raised intracranial pressure: as determined by the treating neurosurgeon, including severe headache, nausea, decreasing level of consciousness, precluding 4-7-day delay in scheduling neurosurgery (i.e., immediate surgery is indicated, and patient cannot wait)
• Prior treatment
• Received bevacizumab (AVASTIN) < 30 days prior to registration
• NOTE: Bevacizumab is allowed for symptom control during the adjuvant phase of the study
• Increasing dexamethasone dose prior to registration
• NOTE: Patients currently on dexamethasone must be on dose ≤ 4 mg/day at time of registration
• Received chemotherapy < 30 days prior to registration
• Received a live vaccine < 30 days prior to registration
• Failure to recover from any adverse events related to any of the following therapies received prior to registration:
• Major surgery < 28 days prior to registration
• Radiation therapy < 14 days prior to registration
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection requiring IV antibiotics
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Or psychiatric illness/social situations (e.g., drug addiction) that would limit compliance with study requirements
• Receiving any other investigational agent at the time of registration
• History of myocardial infarction ≤ 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Active autoimmune disease that has required systemic treatment (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) ≤ 2 years prior to registration
• NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Concurrent known active hepatitis B (i.e., known positive hepatitis B virus \[HBV\] surface antigen \[HBsAg\] reactive) AND known active hepatitis C (i.e., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] detected by polymerase chain reaction \[PCR\]). Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
• NOTE: Patients with known hepatitis B OR hepatitis C may be enrolled if they meet the following criteria:
• Hepatitis B: Patients who are HBsAG positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Patients should remain on anti-viral therapy throughout the treatment phase of the trial and should follow local guidelines for HBV anti-viral therapy after completing study treatment
• Hepatitis C: Patients with history of hepatitis C infection are eligible if HCV viral load is undetectable at screening. Patients must have completed curative anti-viral therapy at least 4 weeks prior to registration
• Known history of active TB (Bacillus tuberculosis)
• History of (non-infectious) pneumonitis or interstitial lung disease that required steroids, or current pneumonitis or interstitial lung disease
• Hypersensitivity to pembrolizumab, IL-2, GI-102 or any of its excipients
• History of allogeneic tissue/solid organ transplant