Nivolumab, with or without ipilimumab, does not provide a clinical benefit in pediatric patients with high-grade central nervous system (CNS) cancer, according to researchers.
In a phase 2 trial, nivolumab alone or in combination with ipilimumab did not improve progression-free survival (PFS) or overall survival (OS), when compared with historical data.
These results were presented at the 20th International Symposium on Pediatric Neuro-Oncology (ISPNO).
With the phase 2 CheckMate 908 study (ClinicalTrials.gov Identifier: NCT03130959), researchers aimed to determine whether nivolumab, with or without ipilimumab, improves outcomes among pediatric patients with high-grade CNS cancer, compared with historical data. The study was not designed to compare the treatment arms directly.
The trial included 166 patients — 85 who were assigned to receive nivolumab alone (3 mg/kg every 2 weeks) and 81 who were assigned to receive nivolumab plus ipilimumab (nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg every 3 weeks for 4 doses, then nivolumab at 3 mg/kg every 2 weeks).
The median age was 10 years (range, 1-21) in the nivolumab arm and 11 years (range, 1-21) in the combination arm. A majority of patients in both arms were male (61.2% in the nivolumab-alone arm and 54.3% in the combination arm). A minority of patients (25.8% vs 19.3%) had PD-L1 expression levels of at least 5%.
Patients were divided into 5 cohorts by tumor type and disease status — newly diagnosed diffuse intrinsic pontine glioma (DIPG) after radiotherapy, recurrent/progressive high-grade glioma/glioblastoma, relapsed/resistant medulloblastoma, relapsed/resistant ependymoma, or other recurrent or progressive high-grade CNS tumors.
The primary endpoint was OS for the DIPG cohort and PFS for the other cohorts. In patients with DIPG, the median OS was 11.7 months with nivolumab and 10.8 months with the combination. The 12-month OS rate was 48% and 42.9%, respectively.
In patients with recurrent/progressive high-grade glioma/glioblastoma, the median PFS was 1.7 months with nivolumab and 1.3 months with the combination. The 6-month PFS rate was 9.4% and 15.4%, respectively.
In patients with relapsed/resistant medulloblastoma, the median PFS was 1.4 month with nivolumab and 2.8 months with the combination. The 6-month PFS rate was 0% and 20%, respectively.
In patients with relapsed/resistant ependymoma, the median PFS was 1.4 months with nivolumab and 4.6 months with the combination. The 6-month PFS rate was 27.3% and 11.4%, respectively.
In patients with other recurrent or progressive high-grade CNS tumors, the median PFS was 1.4 months with nivolumab and 2.8 months with the combination. The 6-month PFS rate was 0% and 20%, respectively.
PFS and OS were not affected by baseline PD-L1 expression.
Treatment-related adverse events (TRAEs) of any grade occurred in 57.6% of patients in the nivolumab arm and 64.2% of those in the combination arm. The rate of grade 3 or higher TRAEs was 14.1% and 27.2%, respectively.
The rate of serious TRAEs was 11.8% in the nivolumab arm and 24.7% in the combination arm. The rate of TRAEs leading to discontinuation was 11.8% and 17.3%, respectively.
Disclosures: This research was supported by Bristol-Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Dunkel IJ, Cohen K, Foreman NK, et al. Nivolumab with or without ipilimumab in pediatric patients with high-grade CNS malignancies: Efficacy, safety, biomarker, and pharmacokinetic results from Checkmate 908. Presented at ISPNO 2022; June 12-15, 2022. Abstract IMMU-08.