The combination of ipilimumab and nivolumab plus radiation therapy did not lead to an improvement in progression-free survival compared with radiation therapy and temozolomide for patients with newly diagnosed MGMT-unmethylated glioblastoma, according to phase II results of the NRG-BN007 trial published in the Journal of Clinical Oncology. As a result of these primary endpoint findings, accrual for the study closed and it will not progress to a phase III study.
“Although ipilimumab and nivolumab did not improve progression-free survival for this specific population, there still remains a dire need to find new therapies for glioblastoma, especially MGMT-unmethylated disease. The results of this trial are incredibly important to inform practice and redirect potential future options for patients with MGMT-unmethylated glioblastoma. Further biomarker analyses are ongoing to determine if any specific subsets do derive benefit from this treatment combination. Follow-up for overall survival also continues,” stated lead study author Andrew B. Lassman, MS, MD, FAAN, FASCO, John Harris Professor and Vice Chair for Clinical Research and Division Chief of Neuro-Oncology in the Neurology Department, Associate Dean of Clinical Research Compliance for the Vagelos College of Physicians & Surgeons at Columbia University, Associate Director for Clinical Trials for the Herbert Irving Comprehensive Cancer Center, and Attending Neurologist, NewYork-Presbyterian.
Study Methods and Rationale
The phase I NRG-BN002 trial had shown that combining ipilimumab and nivolumab with radiation therapy was safe for patients with newly diagnosed glioblastoma, which had led to further study in a phase II/III trial.
The study enrolled 159 patients with newly diagnosed, MGMT-unmethylated glioblastoma and a Karnofsky performance status of at least 70. Participants were randomly assigned to receive either radiotherapy with dual immune checkpoint inhibition with ipilimumab and nivolumab (n = 79) or with temozolomide (n = 80). Patients were stratified by recursive partitioning analysis and intention to use tumor-treating fields.
The primary endpoint was median progression-free survival, with the planned hazard ratio of 0.58 or less at a one-sided significance level of 0.15 in order to demonstrate superiority of the investigational regimen.
Key Study Findings
As of the preplanned phase II analysis, median progression-free survival was 7.7 months in the immunotherapy arm compared with 8.5 months in the temozolomide arm (hazard ratio [HR] = 1.47; 70% confidence interval [CI] = 1.19–1.83; 95% CI = 0.98–2.2; one-sided P = .96).
Overall survival data are still immature with more than 50% of participants still alive, but initial findings showed no signal for a difference between the arms, with a median overall survival of about 13 months in each (HR = 0.95; 95% CI = 0.61–1.49; P = .36).
No new safety signals were identified in the study for the immunotherapy regimen. Further molecular correlative analyses and survival follow-up are ongoing.
Disclosure: The study was funded by grants from the National Cancer Institute and support from Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
