Primary Objectives Cohort 1: To determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of ASP8374 when administered with cemiplimab among recurrent malignant glioma participants. Cohort 2: To determine if neoadjuvant immune checkpoint blockade (ICB) with ASP8374, cemiplimab and the combination of ASP8374 plus cemiplimab will induce a statistically significant increase in CD8+ tumor infiltrating lymphocyte (TIL) density in recurrent glioblastoma (GBM) participants undergoing planned surgery compared controls who do not receive neoadjuvant ICB. Secondary Objectives To estimate the anti-tumor benefit of neoadjuvant immune checkpoint blockade with ASP8374, cemiplimab and the combination of ASP8374 plus cemiplimab as measured by median progression-free survival (PFS) and overall survival (OS) as well as progression-free survival at 6 months (PFS-6) and overall survival at 12 months (OS-12); To evaluate the tolerability and safety profile of ASP8374, cemiplimab and the combination of ASP8374 plus cemiplimab in participants with recurrent GBM To evaluate the safety of repeat doses of 89Zr-Df-IAB22M2C (CD8 PET tracer) Exploratory Objectives To evaluate changes in immune profiling associated with neoadjuvant immune checkpoint blockade for participants in cohorts 2A, 2B and 2C compared to 2D (no neoadjuvant immune checkpoint therapy) including: RNA-seq performed on bulk tumor as well as immune cell subsets including CD3+, CD4+, CD8+ T cells, NK cells, microglia and tumor associated macrophages; TCR clonality; multiplex immunofluorescence; quantitative analysis of immune cell subsets and functional measures of activation/suppression by advanced flow cytometry; and next generation sequencing to assess tumor mutational burden. To investigate biomarkers that may correlate with treatment outcome of ASP8374, cemiplimab and the combination of ASP8374 plus cemiplimab. To assess potential change in 89Zr-Df-IAB22M2C uptake in tumor tissue between baseline and after neoadjuvant immune checkpoint blockade or control therapy. Explore the visual and semi-quantitative 89Zr-Df-IAB22M2C PET measurements with clinical outcome. To objectively evaluate change in neurologic function using the Neurologic Assessment in Neuro-Oncology (NANO) scale. To characterize the pharmacokinetics and immunogenicity profile of ASP8374 when administered as single agent and in combination with cemiplimab.

You may be eligible for this study if you meet the following criteria:

• Conditions: Medical Research
• Age: 99 years or below
• Gender: All