Recruiting

Phase 2

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

Sponsor:

Mayo Clinic

Code:

NCT07301268

Conditions

Glioblastoma, IDH-Wildtype

Progressive Astrocytoma, IDH-Mutant, Grade 4

Progressive Glioblastoma

Progressive Gliosarcoma

Recurrent Astrocytoma, IDH-Mutant, Grade 4

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102

Computed Tomography

Echocardiography Test

Magnetic Resonance Imaging

Study Details

Brief summary:

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.

Conditions

Glioblastoma, IDH-Wildtype

Progressive Astrocytoma, IDH-Mutant, Grade 4

Progressive Glioblastoma

Progressive Gliosarcoma

Recurrent Astrocytoma, IDH-Mutant, Grade 4

Study ID

NCT07301268

Start date

Apr 1, 2026

Status verified date

Apr, 2026

Completion date

Apr 30, 2034

Anticipated

Primary completion date

Apr 30, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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)

Exclusion Criteria:

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

Study Design

Enrollment

36 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Group A (GI-102, pembrolizumab)

Patients receive GI-102 IV over 30-120 minutes on day 1 of cycle 1. Patients undergo surgery at least 14 days after cycle 1 day 1 treatment. Starting with cycle 2, patients may also receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles 2+ repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may receive GI-102 for up to 2 years. Patients also undergo echocardiography or MUGA at screening, as well as blood sample collection and MRI or CT throughout the study.

experimental: Group B (GI-102, pembrolizumab)

Patients receive GI-102 IV over 30-120 minutes and pembrolizumab IV over 30 minutes on day 1 of cycle 1. Patients undergo surgery at least 14 days after cycle 1 day 1 treatment. Patients then receive GI-102 IV over 30-120 minutes and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles 2+ repeat every 21 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. Patients may receive GI-102 for up to 2 years. Patients also undergo echocardiography or MUGA at screening, as well as blood sample collection and MRI or CT throughout the study.

Interventions

Biospecimen Collection

Undergo blood sample collection

Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102

Given IV

Computed Tomography

Undergo CT

Echocardiography Test

Undergo echocardiography

Magnetic Resonance Imaging

Undergo MRI

Multigated Acquisition Scan

Undergo MUGA

Pembrolizumab

Given IV

Surgical Procedure

Undergo surgery

Primary outcome measure

Change in pharmacodynamic markers of interest in tumor tissue [ Time Frame: Up to 2 years ]

Central Contacts and Locations

Central contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Clinical Trials Referral Office

855-776-0015 mayocliniccancerstudies@mayo.edu

Principal Investigator:

Jian L. Campian, MD, PhD

More Information

Sponsor

Mayo Clinic

Last update posted

Apr 8, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-04-08.