NRG-Oncology BN007 Trial (Phase II/III)
Title: A Randomized Study of Ipilimumab plus Nivolumab versus Temozolomide in Newly Diagnosed MGMT-Unmethylated Glioblastoma
In this national, randomized phase II/III trial (NRG-BN007; NCT04396860), adults with newly diagnosed glioblastoma characterized by an unmethylated MGMT promoter were enrolled. Following definitive surgery, patients received radiotherapy combined either with immunotherapy (ipilimumab plus nivolumab) or the standard chemotherapy agent temozolomide (TMZ) .
Purpose
Assess whether dual immune checkpoint inhibition improves progression-free survival (PFS) as compared with standard TMZ. If successful, this would justify advancing to a Phase III stage focused on overall survival (OS) .
Design & Enrollment
Phase II cohort: 159 eligible patients randomized (79 received ipilimumab + nivolumab, 80 received TMZ), stratified by recursive partitioning analysis (RPA) class and intent to use Tumor Treating Fields . Population characteristics: Median age ~60 years, majority male (~66%), and mostly RPA classes IV/V, with balanced surgical and performance status distributions across arms .
Results
Progression-Free Survival (PFS): Ipilimumab + Nivolumab arm: median PFS of 7.7 months (95% CI: 6.5–8.5) TMZ arm: median PFS of 8.5 months (95% CI: 7.1–10.4) Hazard ratio (HR): 1.47 (95% CI: 0.98–2.2), one-sided p = 0.96 — no PFS improvement .
Overall Survival (OS): Data immature (over 50% of patients still alive), with both arms showing similar median OS (~13 months) HR: 0.95 (95% CI: 0.61–1.49), p = 0.36 — no significant OS difference .
Safety: The immunotherapy arm experienced treatment-related grade 3 events in 33.3%, grade 4 in 5.1%, and grade 5 in 2.6% (two patients; one case each of colitis and autoimmune disorder). No new safety concerns were identified overall .
Conclusion
The Phase II analysis clearly demonstrated that ipilimumab plus nivolumab, in combination with radiotherapy, did not improve PFS compared to standard TMZ in patients with MGMT-unmethylated, newly diagnosed glioblastoma. As a result, the trial will not proceed to Phase III. Additional biomarker analyses and OS follow-up are ongoing
