CTIM-21. PEPTIDE VACCINE DIRECTED TO CMV pp65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL

Thompson, Eric; Landi, Daniel; Lipp, Eric; Balajonda, Bea; Herndon, James; Buckley, Evan; Flahiff, Charlene; Jaggers, Denise; Schroeder, Kristin; Randazzo, Dina; Desjardins, Annick; Johnson, Maggie; Peters, Katherine; Khasraw, Mustafa; Malinzak, Michael; Mitchell, Duane; Ashley, David; Sampson, John

doi:10.1093/neuonc/noaa215.155

Abstract

Abstract INTRODUCTION The cytomegalovirus (CMV) antigen, pp65, is ubiquitously expressed in malignant glioma and medulloblastoma but not in healthy brain. The objective of this Phase I trial (NCT03299309) was to assess the safety and feasibility of a novel pp65 peptide vaccine (PEP-CMV) in children and young adults with recurrent medulloblastoma and malignant glioma. METHODS Vaccines contain a synthetic long peptide (SLP) of 26 amino acids encoding multiple potential class I, class II, and antibody epitopes of CMV pp65 across several haplotypes. This SLP is administered as an emulsion in Montanide ISA 51. Patients receive a single course of temozolomide to induce lymphopenia, tetanus/diphtheria toxoid site preconditioning, then vaccines administered intradermally every two weeks for 3 doses, then monthly. RESULTS To date, 17 patients have been enrolled. Diagnoses include medulloblastoma (n=1), glioblastoma (n=9), anaplastic oligodendroglioma (n=2), anaplastic astrocytoma (n=2), and malignant glioma NOS (n=3). Mean number of prior treatment regimens is 4.9 (range 1–12). Mean age is 22yo (range 6–35) and 41% of patients are male. The median KPS is 80. The median number of vaccines given at time of analysis is 3.3 (range 1–12). There have been no ≥ 3 Grade toxicities related to the vaccine. One patient developed nausea, vomiting, palpitations, and tachycardia after vaccination and had elevated inflammatory cytokines consistent with cytokine release syndrome. Median PFS is 2.5 months (95% CI: 0.8, not estimable) and median OS is 6.5 months (95% CI 1.8, not estimable). Interim analysis of immune monitoring bloodwork and perfusion MRI to quantify responses to PEP-CMV has been delayed due to COVID-19. However, adults with GBM who received PEP-CMV (NCT02864368) had significant (p≤0.05) increases in GCSF, GM-CSF, IFN-γ, IL-10, IL-2, IL-8, MIP1-α, and TNF-α levels. CONCLUSIONS Preliminary results demonstrate that PEP-CMV is feasible and well-tolerated in heavily pretreated, multiply recurrent patients.

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https://hdl.handle.net/10161/24048

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10.1093/neuonc/noaa215.155

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Thompson, Eric; Landi, Daniel; Lipp, Eric; Balajonda, Bea; Herndon, James; Buckley, Evan; ... Sampson, John (2020). CTIM-21. PEPTIDE VACCINE DIRECTED TO CMV pp65 FOR TREATMENT OF RECURRENT MALIGNANT GLIOMA AND MEDULLOBLASTOMA IN CHILDREN AND YOUNG ADULTS: PRELIMINARY RESULTS OF A PHASE I TRIAL. Neuro-Oncology, 22(Supplement_2). pp. ii37-ii37. 10.1093/neuonc/noaa215.155. Retrieved from https://hdl.handle.net/10161/24048.

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Scholars@Duke

David Michael Ashley

Rory David Deutsch Distinguished Professor of Neuro-Oncology

My career in cancer research dates more than two decades. I am credentialed in both pediatric and adult neuro-oncology practice and this has been the focus of my efforts in translational research and leadership. As evident from my publication and grant support record, my primary academic focus has been on neurologic tumors, the development of innovative therapies and approaches to care. These efforts have included basic and translational laboratory research. My experience includes moving labo

Margaret Johnson

Assistant Professor of Neurosurgery

I am a neuro-oncologist, neurologist, and palliative care physician at the Preston Robert Tisch Brain Tumor Center. I also provide neuro-oncology expertise for the National Tele-Oncology Program and National Precision Oncology Program at the Veteran's Health Administration. My clinical and research interests encompass supportive care and palliative care with a special interest in older adults with brain tumors. The incidence of malignant brain tumors like glioblastoma and non-malignant tumors li

Mustafa Khasraw

Professor of Neurosurgery

I am a physician-scientist, a medical oncologist, a neuro-oncologist, a tenured professor at the departments of neurosurgery, medicine, and immunology, and Deputy Director of the Center for Cancer Immunotherapy, Duke Cancer Institute, where we are tasked to speed up clinical research and translation for scientists across all departments and all tumor types at Duke, who have made discoveries that show promise for developing new immune and T cell-based therapies. I lead a Tumor Immunobi

Daniel Bryce Landi

Assistant Professor of Pediatrics

John Howard Sampson

Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine

Current research activities involve the immunotherapeutic targeting of a tumor-specific mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches using peptide vaccines and dendritic cells. Another area of interest involves drug delivery to brain tumors. Translational and clinical work is carried out in this area to formulate the relationship between various direct intratu

Kristin M. Schroeder

Associate Professor of Pediatrics

I have a strong belief that all children diagnosed with cancer should have the same chance of cure regardless of where they live. Since 2014, i have spent six or more months per year in Mwanza, Tanzania, at the Bugando Medical Centre as part of the Duke Global Cancer Program. In addition to developing capacity for pediatric cancer care, my research focuses on creating interventions to improve outcomes and reducing treatment abandonment in low resource settings. As a trained pedi

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