CTIM-15 - Results of a Phase Ib Trial of Recombinant Polio:rhinovirus Immunotherapy for Recurrent Pediatric High Grade Glioma

Friday, November 18, 2022

10:45 AM – 10:55 AM ET

Location: Ballroom A

Oral Abstract Presenter(s)

Eric M. Thompson, MD

Duke University Medical Center
DURHAM, United States

Author(s)

Daniel B. Landi, MD

Duke University Medical Center
Durham, United States
Michael C. Brown, PhD

Duke University
Durham, United States
HF

Henry S. S. Friedman, MD

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
Durham, United States
RM

Roger E. McLendon, MD

Duke University Medical Center
Durham, United States
DB

Dani Bolognesi

Duke University Medical Center
Durham, United States
KS

Kristin Schroeder

Duke University Medical Center
Durham, United States
OB

Oren Becher

Mt. Sinai Health System
New York, United States
AF

Allan H. Friedman, M.D.

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
Durham, United States
AW

Ashley Walter

Duke University Medical Center
Durham, United States
ST

Stevie Threatt

Duke University Medical Center
Durham, United States
DJ

Denise Jaggers, RN, BSN

Duke University Medical Center
Durham, United States
Annick Desjardins, MD, FRCPC (she/her/hers)

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center
Durham, United States
MG

Matthias Gromeier, MD

Duke University Medical Center
Durham, United States
DB

Darell D. Bigner, MD, PhD

Duke University Medical Center
Durham, United States
David M. Ashley, MBBS (Hon), FRACP, PhD

The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA
Durham, United States

Background: Outcomes of recurrent pediatric high grade glioma (pHHG) are poor with a median overall survival (OS) of < 6 months. Viral immunotherapy such as the polio:rhinovirus chimera, PVSRIPO, is a novel treatment approach for recurrent pHHG. PVSRIPO is genetically engineered to prevent neurovirulence. In adults with recurrent glioblastoma treated with PVSRIPO, 21% survived > 36 months. The poliovirus receptor, CD155, is ubiquitously expressed in malignant pediatric brain tumors including pHHG.

Methods: The primary objective of this Phase 1b clinical trial was to evaluate the safety and feasibility of PVSRIPO for recurrent pHGG. PVSRIPO was given at a single dose, 5x10⁷ 50% tissue-culture infectious dose (TCID₅₀) administered by convection enhanced delivery (CED) to children with biopsy-confirmed recurrent pHHG between ≥ 1 and ≤ 5.5 in diameter. 3 mL of PVSRIPO was delivered at 0.5 mL/hr via a single catheter.

Results: Eight patients were treated with PVSRIPO including 5 males and 3 females with a median age of 16.5 (range 9-19). Six patients had recurrent glioblastoma, 2 had recurrent anaplastic astrocytoma. The median number of previous recurrences prior to enrollment was 3.5 (range 1-5). Four patients received bevacizumab on-study for treatment-related peritumoral inflammation/edema. Six of 8 patients experienced 26 treatment related adverse events (AEs) possibly, probably, or definitely related to protocol treatment. There were no Grade 4 or 5 AEs. There were 3 Grade 3 AEs: 2 headaches and 1 seizure. There were no AEs related to biopsy or CED catheter insertion/removal. Median OS was 4.13 months (range 1.23-NA). One patient is currently alive at > 21 months. Monocyte and T cell inflammatory phenotypes and total CD4+ T cells were increased in peripheral blood after treatment.

Conclusions: CED of PVSPRIO is both safe and feasible for the treatment of recurrent pHHG. Histologic correlative results will also be presented.