A peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma: a phase 1 trial

Eric M Thompson; David M Ashley; Katayoun Ayasoufi; Pamela Norberg; Gerald Archer; Evan D Buckley; James E Herndon 2nd; Ashley Walter; Bridget Archambault; Charlene Flahiff; Denise Jaggers; Laura Gorski; Luis A Sanchez; Kendra Congdon; Kelly Hotchkiss; Sarah L Cook; Eliese Moelker; Gordana Vlahovic; Elizabeth Reap; Kristin Schroeder; Dina Randazzo; Annick Desjardins; Margaret O Johnson; Katherine Peters; Mustafa Khasraw; Henry Friedman; Duane A Mitchell; John H Sampson; Daniel Landi

doi:10.1038/s43018-025-00998-z

A peptide vaccine targeting the CMV antigen pp65 in children and young adults with recurrent high-grade glioma and medulloblastoma: a phase 1 trial

Nat Cancer. 2025 Jun 12. doi: 10.1038/s43018-025-00998-z. Online ahead of print.

Authors

Eric M Thompson^{1

2

3

4}, David M Ashley^{5

6}, Katayoun Ayasoufi^{5

6}, Pamela Norberg^{5

6}, Gerald Archer^{5

6}, Evan D Buckley⁷, James E Herndon 2nd⁸, Ashley Walter⁶, Bridget Archambault⁹, Charlene Flahiff⁶, Denise Jaggers⁶, Laura Gorski⁶, Luis A Sanchez⁵, Kendra Congdon⁵, Kelly Hotchkiss⁵, Sarah L Cook⁵, Eliese Moelker⁵, Gordana Vlahovic⁶, Elizabeth Reap⁵, Kristin Schroeder^{6

9}, Dina Randazzo^{5

6}, Annick Desjardins^{5

6}, Margaret O Johnson^{5

6}, Katherine Peters^{5

6}, Mustafa Khasraw^{5

6}, Henry Friedman^{5

6}, Duane A Mitchell¹⁰, John H Sampson^{5

6}, Daniel Landi^{6

9}

Affiliations

¹ Department of Neurological Surgery, Duke University, Durham, NC, USA. t.eric@wustl.edu.
² Department of Neurological Surgery, The University of Chicago, Chicago, IL, USA. t.eric@wustl.edu.
³ Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA. t.eric@wustl.edu.
⁴ Department of Neurological Surgery, Washington University, St. Louis, MO, USA. t.eric@wustl.edu.
⁵ Department of Neurological Surgery, Duke University, Durham, NC, USA.
⁶ Preston Robert Tisch Brain Tumor Center, Duke University, Durham, NC, USA.
⁷ Duke Cancer Institute Biostatistics, Duke University, Durham, NC, USA.
⁸ Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
⁹ Department of Pediatrics, Duke University, Durham, NC, USA.
¹⁰ Department of Neurological Surgery, The University of Florida, Gainesville, FL, USA.

PMID: 40506525
DOI: 10.1038/s43018-025-00998-z

Abstract

The human cytomegalovirus (CMV) antigen pp65 is expressed in high-grade glioma (HGG) and medulloblastoma but not in the adjacent brain. This single-arm phase 1 trial ( NCT03299309 ) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targeting pp65 in individuals (3-35 years old) with recurrent HGG or medulloblastoma. Thirty-six individuals with HGG received PEP-CMV. The mean age was 22.75 ± 9.34 years. The primary outcome, percentage of unacceptable toxicity, was met. The maximum-grade adverse events (AE) related to PEP-CMV were 17 grade 1 AEs, 15 grade 2 AEs, 1 grade 3 AE (pyramidal tract syndrome) and 1 grade 4 AE (cerebral edema). As a secondary outcome, in 21 individuals with evaluable data, T cell reactivity, measured as change in baseline interferon-γ pp65 enzyme-linked immunospot assay reactivity, had an estimated increase of 46 spots (95% confidence interval (95% CI): 8, 194) after treatment with PEP-CMV. As exploratory endpoints, the median progression-free survival was 2.5 months (95% CI: 2.2, 3.2), and median overall survival was 6.5 months (95% CI: 4.6, 8.4). PEP-CMV is well tolerated and elicits an antigen-specific immune response in individuals with multiply recurrent HGG. Only two individuals with medulloblastoma were enrolled, showing one grade 3 encephalopathy possibly related to PEP-CMV, while neither had postvaccine immune assessments due to progression-free survival and overall survival less than 2 months.