Glioblastoma, IDH-WildtypePhase 2NCT07301268
GI-102 Alone or With Pembrolizumab Before Surgery for Treatment of Recurrent or Progressive IDH Wildtype Glioblastoma and IDH Mutated Grade 4 Astrocytoma
A Phase 2 study testing Biospecimen Collection, Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102 and Computed Tomography in people with Glioblastoma, IDH-Wildtype and Progressive Astrocytoma, IDH-Mutant, Grade 4, run by Mayo Clinic at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, IDH-Wildtype, Progressive Astrocytoma, IDH-Mutant, Grade 4, Progressive Glioblastoma
- What is being tested?
- Biospecimen Collection, Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102 and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2026to 1 Sep 2032
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Jian L. Campian, MD, PhD
About this study
Official title: 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.
- Conditions
- Glioblastoma, IDH-Wildtype, Progressive Astrocytoma, IDH-Mutant, Grade 4, Progressive Glioblastoma, Progressive Gliosarcoma, Recurrent Astrocytoma, IDH-Mutant, Grade 4, Recurrent Glioblastoma, IDH-Wildtype
- Being tested
- Biospecimen Collection, Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102, Computed Tomography, Echocardiography Test, Magnetic Resonance Imaging
- Medical subject headings
- Glioblastoma, Astrocytoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102Drug
Also called GI 102, GI-102, GI102
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Echocardiography TestProcedure or surgery
Also called EC, Echocardiography
Undergo echocardiography
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
Multigated Acquisition ScanProcedure or surgery
Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan
Undergo MUGA
PembrolizumabBiological
Also called BCD-201, GME 751, GME751, Keytruda
Given IV
Surgical ProcedureProcedure or surgery
Also called Operation, Surgery, Surgery Type, Surgery, NOS
Undergo surgery
| Study group | Role | What they receive |
|---|---|---|
| Group A (GI-102, pembrolizumab) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Drug: Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Biological: Pembrolizumab; Procedure: Surgical Procedure |
| Group B (GI-102, pembrolizumab) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Drug: Bispecific CD80-lgG4Fc-IL-2v Fusion Protein GI-102; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Biological: Pembrolizumab; Procedure: Surgical Procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pharmacodynamic markers of interest in tumor tissue
Focused on an increase in CD8 T cell infiltration as well as a decrease in regulatory T cells in the tumor microenvironment (TME). Samples from stereotactic needle biopsy (pre-treatment) and resection (post-treatment) will be compared. For analyses looking at changes in measures before vs. after treatment, a paired sample t-test (or nonparametric Wilcoxon signed rank test if not sufficiently normally distributed) will have 80% power to detect an effect size of d = 0.675 within a treatment group (i.e. n=15 patients), and using a one-sided α of 0.05. Our utilization of a one-sided test in this setting is based on the fact that for changes before vs. after treatment, we are specifically focused on targeting an increase in CD8 T cell infiltration as well as a decrease in regulatory T cells in the TME.
Measured: Up to 2 years
Secondary outcomes (2)
Overall survival (OS)
Defined as the time from date of treatment start to date of death from any cause
Measured: Up to 5 years
Incidence of adverse events (AEs)
Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Will be evaluated and summarized based on the maximum grade for each type of AE reported along with the perceived attribution of the AE to the study treatment.
Measured: Up to 90 days after last dose of study treatment (an average of 2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2025
- Study start3 Aug 2026
- Primary completion1 Sep 2029 (estimated)
- Study completion1 Sep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma, IDH-WildtypeStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jian L Campian, MD, PhD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07301268
- Sponsor's protocol ID
- MC230719
- Other IDs
- NCI-2025-09081, 25-002007, MC230719
- Status last verified
- Sep 2026
- First submitted
- 22 Dec 2025
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No