NRG ONCOLOGY STUDY BN007: RANDOMIZED PHASE II/III TRIAL OF IPILIMIUMAB (IPI) PLUS NIVOLUMAB (NIVO) VS. TEMOZOLOMIDE (TMZ) IN MGMT-UNMETHYLATED (UMGMT) NEWLY DIAGNOSED GLIOBLASTOMA (NGBM)
Recommended Citation
Lassman A, Polly M, Iwamoto F, Sloan A, Wang T, Aldape K, Wefel J, Gondi V, Gutierrez A, Manasawala M, Gilbert M, Sulman E, Wolchok J, Green R, Neil E, Lukas R, Goldlust S, Snuderl M, Dignam J, Won M, Movsas B, Mehta M. NRG ONCOLOGY STUDY BN007: RANDOMIZED PHASE II/III TRIAL OF IPILIMIUMAB (IPI) PLUS NIVOLUMAB (NIVO) VS. TEMOZOLOMIDE (TMZ) IN MGMT-UNMETHYLATED (UMGMT) NEWLY DIAGNOSED GLIOBLASTOMA (NGBM). Neuro-Oncology 2023; 25:ii2.
Document Type
Conference Proceeding
Publication Date
9-8-2023
Publication Title
Neuro-Oncology
Keywords
adjuvant, biological marker, corticosteroid, nivolumab, temozolomide, adult, autoimmune disease, cancer adjuvant therapy, cancer surgery, cancer survival, clinical trial, colitis, conference abstract, controlled study, demographics, diagnosis, drug efficacy, drug safety, drug therapy, follow up, glioblastoma, glioma, Hispanic, histology, histopathology, human, human tissue, major clinical study, male, overall survival, phase 2 clinical trial, phase 3 clinical trial, randomized controlled trial, recursive partitioning
Abstract
BACKGROUND: New therapies are especially needed for uMGMT nGBM. NRG Oncology BN002 (phase I) demonstrated safety and preliminary efficacy of Ipi+Nivo for nGBM, leading to BN007 as phase II/III. METHODS: Adults with uMGMT nGBM (WHO 2016) and KPS ≥ 70 were randomized to RT and concurrent and adjuvant Ipi+Nivo or TMZ, stratified by glioma-recursive partitioning analysis class (RPA), intent to use tumortreating fields (NCT04396860). Phase II primary endpoint was progressionfree survival (PFS), powered 95% to detect a hazard ratio (HR) ≤0.58 with 1-sided 0.15 significance after 100 events. If p<0.15, then phase III would accrue with overall survival (OS) as primary endpoint. Corticosteroids were disallowed at Ipi+Nivo start. Histology, biomarkers, and PFS were assessed centrally. RESULTS: Among 374 patients screened, 159 were randomized in phase II (79 Ipi+Nivo, 80 TMZ). Demographics (age median 60 years, range 28-79; male 66%, white 88%, not Hispanic/Latino 89%), KPS (90- 100 61%), extent of resection (gross total 65% per local PI), and RPA (III 10%, IV 73%, V 17%) were well-balanced between arms. After 100 PFS events, the pre-planned phase II analysis demonstrated no improvement for Ipi+Nivo vs. TMZ [median 7.7 (95% CI: 6.5, 8.5) vs. 8.5 (95% CI: 7.1, 10.4) months; HR 1.47 (95% CI: 0.98-2.2); 1-sided p=0.96]. OS is immature (>50% alive, 13.7 months median follow-up) but without observed difference between arms [median ∼13 months each; HR 0.95 (95% CI: 0.61-1.49); 1-sided p=0.36]. On the Ipi+Nivo arm, treatment-related grade 3, 4, and 5 events were reported in 26 (33.3%), 4 (5.1%), and 2 (2.6%; colitis and autoimmune disorder, n=1 each) patients. CONCLUSION: Ipi+Nivo did not improve PFS for uMGMT nGBM. Accrual permanently closed after phase II. No new safety signals were identified. Molecular analyses and survival follow-up are ongoing.
Volume
25
First Page
ii2
