MC230719 Window Of Opportunity Study Of GI-102 In Patients With Recurrent High-Grade Glioblastoma
This phase II trial compares the effect of GI-102 alone and in combination with pembrolizumab given before surgery in treating patients with IDH wildtype glioblastoma and IDH mutated grade 4 astrocytoma that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). Glioblastoma is the most common and the most aggressive primary brain tumor in adults. Current standard of care includes surgical resection, radiation and chemotherapy. Treatment is often given before surgery (neoadjuvant therapy) to shrink the tumor and make it easier to remove. Treatment with GI-102, a bispecific fusion protein, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving GI-102 alone and in combination with pembrolizumab between neoadjuvant therapy and surgery may be safe, tolerable, and effective in treating patients with recurrent or progressive IDH wildtype glioblastoma and IDH mutated grade 4 astrocytoma.
• Age ≥ 18 years
• Disease characteristics
‣ Tissue-confirmed progressive or recurrent World Health Organization (WHO) grade IV IDH wildtype glioblastoma (including molecular glioblastoma and gliosarcoma); and IDH mutated WHO grade 4 astrocytoma
⁃ Candidates for surgical resection
• Measurable or non-measurable disease as defined by Response Assessment in Neuro-Oncology (RANO) 2.0
• Willing to undergo clinically indicated biopsy followed by resection of high-grade glioma at Mayo Clinic in Rochester, Minnesota (MN)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0,1, or 2 and Karnofsky performance status (KPS) ≥ 60
‣ NOTE: PS must be assessed (again) ≤ 7 days prior to first dose of study drug
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 15 days prior to registration)
• Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 15 days prior to registration)
• Platelet count ≥ 100,000/mm\^3 (obtained ≤ 15 days prior to registration)
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (per institutional standard) must be ≥ 45 ml/min (obtained ≤ 15 days prior to registration)
• Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels \> 1.5 x ULN (obtained ≤ 15 days prior to registration)
• Aspartate transaminase (AST) AND alanine transaminase (ALT) ≤ 2.5 x ULN (obtained ≤ 15 days prior to registration)
• Amylase and lipase ≤ ULN (obtained ≤ 15 days prior to registration)
• Left ventricular ejection fraction (LVEF) ≥ 50% (obtained ≤ 29 days prior to registration)
• Negative pregnancy test done ≤ 8 days prior to registration, for persons of childbearing potential only
• Persons of childbearing potential (POCBP) or able to father a child must be willing to use adequate contraception starting with first dose through 180 days after last dose
• Provide written informed consent
• Willingness to provide blood specimens for correlative research
• Willingness to provide tissue specimens for correlative research
• Willingness to provide written informed consent for the neuro-oncology biorepository (IRB 12-003458) for archiving of tissue, cerebrospinal fluid (CSF), and/or blood samples collected on this protocol
• Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)