EPCT-01. A NOVEL 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

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, 22 patients have been enrolled. Diagnoses include medulloblastoma (n=2), glioblastoma (n=12), anaplastic oligodendroglioma (n=2), anaplastic astrocytoma (n=3), 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 45% 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: 1.7,4.5) and median OS is 6.5 months (95% CI 3.3, 7.9). Immune response to pp65 as determined by ELISpot was found in 75% of patients. On MRI 6 of the 11 evaluable patients have had at least stable disease with three of those having a partial response. Conclusions Preliminary results demonstrate that PEP-CMV is well-tolerated and elicits an immune response in heavily pretreated, multiply recurrent patients. A multi-institutional Phase II trial is scheduled to open fall 2021.

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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 ◽

10.1093/neuonc/noaa215.155 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii37-ii37

Author(s):

Eric Thompson ◽

Daniel Landi ◽

Eric Thompson ◽

Eric Lipp ◽

Bea Balajonda ◽

...

Keyword(s):

Young Adults ◽

Phase I ◽

Malignant Glioma ◽

Phase I Trial ◽

Peptide Vaccine ◽

Median Number ◽

Immune Monitoring ◽

Preliminary Results ◽

Treatment Regimens ◽

Children And Young Adults

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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EPCT-13. CMV PP65 RNA-PULSED DENDRITIC CELL VACCINES FOR PEDIATRIC GLIOBLASTOMA AND MEDULLOBLASTOMA: PHASE I TRIAL RESULTS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.136 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii306-iii306

Author(s):

Daniel Landi ◽

Gary Archer ◽

Timothy Driscoll ◽

Eric Lipp ◽

Bridget Archambault ◽

...

Keyword(s):

Dendritic Cell ◽

Phase I ◽

Malignant Glioma ◽

Phase I Trial ◽

Active Immunization ◽

Monocyte Differentiation ◽

Dendritic Cell Vaccines ◽

Dc Vaccines ◽

Subsequent Phase ◽

Children And Young Adults

Abstract BACKGROUND Recurrent medulloblastoma and malignant glioma are lethal tumors that are virtually incurable. The cytomegalovirus (CMV) antigen pp65 is ubiquitously expressed on medulloblastoma and malignant glioma but not on healthy brain. We evaluated autologous CMV pp65 RNA-pulsed dendritic cell (DC) vaccines in children and young adults in a phase I trial. METHODS Circulating monocytes were harvested using leukapheresis, differentiated into DCs, matured, and pulsed with pp65 RNA using electroporation. DCs were packaged into vaccines (2x107DC/vaccine) and administered intradermally following tetanus-diphtheria toxoid site preconditioning every 2 weeks x3, then monthly. The primary objectives of the study were to establish the feasibility of generating at least 3 vaccines and safety. An exploratory objective was to evaluate the ability of vaccination to create and enhance patient pp65-specific T cell responses. RESULTS Eleven patients were enrolled with medulloblastoma (n=3) or glioblastoma (n=8). Ages ranged from 9–30 years old (mean 15.5y). Ten of 11 patients (91%) generated at least 3 vaccines (mean 6.2). Eight patients received at least 3 vaccines. To date, 4 patients have received all generated vaccines without progression, 4 patients have progressed, and 2 patients are still receiving vaccines. There have not been any severe adverse events probably or definitely related to vaccines. More mature data will be presented at ISPNO. CONCLUSIONS Leukapheresis and monocyte differentiation is a feasible strategy for generating adequate DCs for active immunization in children with malignant brain tumors. CMV pp65 RNA-pulsed DCs are well-tolerated and immunogenic. Efficacy endpoints will be evaluated in a subsequent phase II trial.

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