Phase 1 Trial of Hypofractionated Stereotactic Re-Irradiation in Combination With Nivolumab, Ipilimumab, and Bevacizumab for Recurrent High-Grade Gliomas

Authors

Solmaz Sahebjam
Raju R Raval
Peter A Forsyth
Heiko Enderling
Nam D Tran
John A Arrington
Robert Macaulay
Haley K Perlow
Joshua D Palmer
Jayeeta Ghose
Prajwal Rajappa
Pierre Giglio
Zihai Li
Arnold B Etame
Sepideh Mokhtari
Ruben J Cruz-Chamorro
Menal Bhandari
Ram Thapa
Timothy J Robinson
Dung-Tsa Chen
Hsiang-Hsuan Michael Yu

Publication Date

1-1-2025

Journal

Neuro-Oncology Advances

Abstract

Background: Our previous clinical investigation suggested that hypofractionated stereotactic re-irradiation (HFSRT) and PD-1 blockade may act synergistically to enhance the immune response against glioma. This subsequent trial investigated the dual blockade of CTLA4 and PD-1 in combination with HFSRT and bevacizumab.

Methods: This phase I study enrolled eligible patients with bevacizumab-naïve recurrent glioblastoma or anaplastic astrocytoma. Participants received nivolumab, ipilimumab, and bevacizumab concurrently with HFSRT (3000 cGy in 5 fractions). Subsequently, nivolumab, ipilimumab, and bevacizumab were administered for a total of 4 cycles followed by nivolumab and bevacizumab until progression. The primary end point of this study was the safety and tolerability of HFSRT in combination with nivolumab, ipilimumab, and bevacizumab in patients with recurrent HGGs. Secondary end points included 6-month survival and 9-month survival.

Results: Twenty-six patients were treated. Treatment-related adverse events (TRAEs) of grade 3 or 4 were observed in 12 (48%) evaluable patients with no unexpected TRAEs. Six months and 9 months survival were 92% (95% CI, 82-100%) and 75% (95% CI, 60-95%), respectively. The median progression-free survival and overall survival were 7.1 months (95% CI, 5.2-12.2) and 15.6 months (95% CI, 11.3-27.0), respectively.

Conclusions: The combination of HFSRT with ipilimumab, nivolumab, and bevacizumab is safe. Our results underscore the potential synergies between stereotactic re-irradiation and checkpoint immunotherapy in patients with recurrent high-grade gliomas.

Keywords

glioblastoma, high-grade glioma, ipilimumab, nivolumab, stereotactic re-irradiation

DOI

10.1093/noajnl/vdaf033

PMID

40134851

PMCID

PMC11934552

PubMedCentral® Posted Date

2-8-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes