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

ConditionsGlioblastoma, IDH-WildtypeProgressive Astrocytoma, IDH-Mutant, Grade 4Progressive GlioblastomaProgressive GliosarcomaRecurrent Astrocytoma, IDH-Mutant, Grade 4Recurrent Glioblastoma, IDH-WildtypeRecurrent GliosarcomaResectable AstrocytomaResectable Glioblastoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMayo Clinic

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

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

    Drug

    Given IV

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Echocardiography Test

    Procedure/Surgery

    Undergo echocardiography

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Surgical Procedure

    Procedure/Surgery

    Undergo surgery

Treatment groups

36 Participants
are divided into 2 treatment groups
Group A: Group A (GI-102, pembrolizumab)Experimental treatment 8 interventions
Group B: Group B (GI-102, pembrolizumab)Experimental treatment 8 interventions

Trial outcomes

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.

Time frame
Up to 2 years

Secondary outcomes

1

Overall survival (OS)

Defined as the time from date of treatment start to date of death from any cause

Time frame
Up to 5 years
2

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.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Mayo Clinic

Lead sponsor

Source ClinicalTrials.gov
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