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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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)

You cannot join if

• 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

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

bispecific CD80-lgG4Fc-IL-2v fusion protein GI-102. A bi-specific Fc fusion protein composed of the N-terminal ectodomain of human CD80 (B7.1) fused to a human immunoglobulin G4 (IgG4) Fc fragment and linked to an interleukin (IL)-2 variant (IL-2v) as a C-terminal moiety, with potential immunostimulatory, immune checkpoint inhibitory and antineoplastic activities. Upon administration of bispecific CD80-IgG4Fc-IL-2v fusion protein GI-102, the CD80 moiety targets and binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4) expressed on T cells. This prevents the binding of CTLA-4 to endogenous CD80, enables the binding of CD80 to CD28, which leads to CD28-mediated signaling, and results in the activation of T cells in the tumor microenvironment (TME). This promotes T-cell activity. The IL-2v moiety may stimulate a local immune response and activate natural killer (NK) cells and cytotoxic T cells. This may enhance the activity of neoantigen specific T cells and potentiates the T-cell-mediated immune response against tumor cells. CD80 is a co-stimulatory molecule expressed on activated antigen presenting cells (APCs) that plays a key role in T-cell activation upon binding to CD28 on T cells. On the other hand, binding of CD80 to CTLA-4 prevents CD80-CD28 engagement, thereby inhibiting T-cell activity and immune activation. CTLA-4 is a member of the immunoglobulin superfamily (IgSF) and an inhibitory molecule upregulated by T cells following T-cell activation. It plays a key role in the downregulation of the immune system. The IL-2v moiety cannot bind to IL-2 receptor-alpha (CD25, IL2Ra) and does not activate regulatory T cells (Tregs). NCI Drug Dictionary

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

Treatments listed in the registry

• Biospecimen Collection (Procedure): Undergo blood sample collection
• Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102 (Drug): Given IV
• Computed Tomography (Procedure): Undergo CT
• Echocardiography Test (Procedure): Undergo echocardiography
• Magnetic Resonance Imaging (Procedure): Undergo MRI
• Multigated Acquisition Scan (Procedure): Undergo MUGA
• Pembrolizumab (Biological): Given IV
• Surgical Procedure (Procedure): Undergo surgery

Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• blood samples: Part of the study plan
• CT scans: Part of the study plan
• MRI: Part of the study plan
• echocardiogram: Part of the study plan
• surgery: Part of the study plan

Main goals

• Change in pharmacodynamic markers of interest in tumor tissue (Up to 2 years)

Other goals

• Overall survival (OS)
• Incidence of adverse events (AEs)

Planned enrollment: 36 (estimated).

• Mayo Clinic in Rochester, Rochester, Minnesota

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07301268
• NCI Drug Dictionary: C200811
• NCI Drug Dictionary: C106432

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 30, 2026. Public record; not medical advice.