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

NCT07301268 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: MC230719NCI-2025-0908125-002007
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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; Recurrent Glioblastoma, IDH-Wildtype; Recurrent Gliosarcoma; Resectable Astrocytoma; Resectable Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 2 years

Secondary Outcomes (2)

• Overall survival (OS)

  Up to 5 years

• Incidence of adverse events (AEs)

  Up to 90 days after last dose of study treatment (an average of 2 years)

Study Arms (2)

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.

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.

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

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

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

Given IV

Also known as: GI 102, GI-102, GI102

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: 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

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: 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

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: 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

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: 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

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Surgical Procedure PROCEDURE

Undergo surgery

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Group A (GI-102, pembrolizumab); Group B (GI-102, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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)

You may not qualify 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Gliosarcoma

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; pembrolizumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jian L Campian, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trials Referral Office

CONTACT

855-776-0015; mayocliniccancerstudies@mayo.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2025
• First Posted: December 24, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2034
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)