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

NCT ID: NCT07301268

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-29

Study Completion Date

2034-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Glioblastoma, IDH-Wildtype Progressive Astrocytoma, IDH-Mutant, Grade 4 Progressive Glioblastoma Progressive Gliosarcoma Recurrent Astrocytoma, IDH-Mutant, Grade 4 Recurrent Glioblastoma, IDH-Wildtype Recurrent Gliosarcoma Resectable Astrocytoma Resectable Glioblastoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

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

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Echocardiography Test

Intervention Type PROCEDURE

Undergo echocardiography

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Surgical Procedure

Intervention Type PROCEDURE

Undergo surgery

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

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

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Echocardiography Test

Intervention Type PROCEDURE

Undergo echocardiography

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Multigated Acquisition Scan

Intervention Type PROCEDURE

Undergo MUGA

Pembrolizumab

Intervention Type BIOLOGICAL

Given IV

Surgical Procedure

Intervention Type PROCEDURE

Undergo surgery

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

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

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Echocardiography Test

Undergo echocardiography

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

Intervention Type PROCEDURE

Pembrolizumab

Given IV

Intervention Type BIOLOGICAL

Surgical Procedure

Undergo surgery

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection GI 102 GI-102 GI102 CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography EC Echocardiography Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Blood Pool Scan Equilibrium Radionuclide Angiography Gated Blood Pool Imaging Gated Heart Pool Scan MUGA MUGA Scan Multi-Gated Acquisition Scan Radionuclide Ventriculogram Scan Radionuclide Ventriculography RNV Scan RNVG SYMA Scanning Synchronized Multigated Acquisition Scanning BCD-201 GME 751 GME751 Keytruda Lambrolizumab MK 3475 MK-3475 MK3475 Pembrolizumab Biosimilar BCD-201 Pembrolizumab Biosimilar GME751 Pembrolizumab Biosimilar QL2107 Pembrolizumab Biosimilar RPH-075 Pembrolizumab Biosimilar SB27 QL2107 RPH 075 RPH-075 RPH075 SB 27 SB-27 SB27 SCH 900475 SCH-900475 SCH900475 Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jian L Campian, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Countries

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United States

Central Contacts

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Clinical Trials Referral Office

Role: CONTACT

Phone: 855-776-0015

Email: [email protected]

Facility Contacts

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Clinical Trials Referral Office

Role: primary

Related Links

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Other Identifiers

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MC230719

Identifier Type: -

Identifier Source: org_study_id

NCI-2025-09081

Identifier Type: REGISTRY

Identifier Source: secondary_id

25-002007

Identifier Type: OTHER

Identifier Source: secondary_id

MC230719

Identifier Type: OTHER

Identifier Source: secondary_id