Immu-26. Safety and Efficacy of Pvsripo in Recurrent Glioblastoma: Long-term Follow-up and Initial Multicenter Results
Year: 2021
Type: conference-abstract
Abstract: BACKGROUND Recurrent glioblastoma (rGBM) is rapidly fatal (median overall survival [mOS] of ~9 months; OS at 12 months [OS12] < 35%) with approved therapies (lomustine±bevacizumab). PVSRIPO is an intratumoral immunotherapy targeting CD155 on antigen-presenting and malignant cells of solid tumors. Preclinically, PVSRIPO delivers a systemic, tumor antigen-specific, polyfunctional T-cell mediated anti-tumor response. Interim, single-center, phase (Ph) 1 results showed greater long-term survival with PVSRIPO vs. criteria-matched external control rGBM patients (Desjardins 2018). Updates to Ph1 safety (at the Ph2 dose) and efficacy and interim multicenter (Ph2) results are presented. METHODS Adults with histologically-confirmed rGBM, Karnofsky performance status ≥ 70, and an active, supratentorial, contrast-enhancing lesion (1-5.5cm) received PVSRIPO (5x107 TCID50) intratumorally via convection-enhanced delivery on Day 1, with a planned follow-up of 24 months. Safety (treatment-emergent adverse events [TEAEs]), efficacy (reported as OS12, OS24, mOS), and blood/tissue were assessed. RESULTS 149 patients (>90% with 1-2 prior progressions, including failure of SOC and patients with prior bevacizumab failure) received the Ph2 dose of PVSRIPO (n=30 received other doses in Ph1 with safety summarized previously). Follow-up durations for surviving patients were 51-74 months (Ph1) and 10-44 months (Ph2). No dose-limiting toxicities occurred; up to 97% of patients experienced mostly grade 1-2 related TEAEs; ≤ 23% patients experienced grade ≥ 3 related events. Neurologic symptoms related to peritumoral edema were most common ( > 90% patients) and were effectively managed with low-dose bevacizumab/corticosteroids. Survival estimates were: OS12: 54%, 50%; OS24: 18%, 17%; mOS: 12.3 (95% CI 10,15.3), 12 (10.6,13.7) months, for the Ph1 and Ph2 trials, respectively. Baseline correlates of longer survival included smaller lesions and methylated MGMT-promoter status. CONCLUSIONS The multicenter/Ph2 study replicated the single-center/Ph1 results. Relative to published data with approved therapies, PVSRIPO was associated with greater long-term survival and mOS in patients with rGBM and was generally well-tolerated.
Source: Neuro-Oncology
Authors: Annick Desjardins, Matthias Gromeier, Henry Friedman, Daniel Landi, Allan Friedman, David M Ashley, William Curry, Nicholas Butowski, Andrew Sloan, Patrick Wen, Robert Cavaliere, Elizabeth Gerstner, Mitchel Berger, Robin Buerki, E Antonio Chiocca, Eric Sauvageau, Andrea Kelly, W Garrett Nichols, Lori Mixson, Adam Dickinson, Kristin Orr, Chris Learn, Darell Bigner
Institutions: Duke University, Duke University Health System, Massachusetts General Hospital, University of California, San Francisco, University Hospitals Cleveland Medical Center, University Hospitals Seidman Cancer Center, Harvard University, Baptist MD Anderson Cancer Center, Brigham and Women's Hospital
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3217007193