NRG Oncology recently reported the results of the National Cancer Institute sponsored phase II/III NRG-BN007 clinical trial showing that combining ipilimumab and nivolumab with radiation therapy (RT) did not improve progression-free survival (PFS) for patients with newly diagnosed MGMT-unmethylated (uMGMT) glioblastoma in comparison to standard RT with temozolomide (TMZ).

Accordingly, this trial will not progress to a phase III.

These results were recently published in the Journal of Clinical Oncology.

NRG-BN007 is the successor trial to the phase I NRG-BN002 clinical study that initially indicated combining ipilimumab and nivolumab with radiation therapy was safe for patients with newly diagnosed glioblastoma.

Glioblastoma is the most common primary cancer of the brain in adults and prognosis is poor despite aggressive treatment with cytoreductive surgery then radiotherapy and temozolomide (TMZ) chemotherapy with or without Tumour Treating Fields.

Additionally, tumours with an uMGMT promoter represent the majority of cases for newly diagnosed glioblastoma and are particularly aggressive, and relatively resistant to temozolomide which has remained the standard first-line chemotherapy for this patient population for the last twenty years.

“Although ipilimumab and nivolumab did not improve PFS 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 uMGMT 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 Andrew B.

Lassman, MS, MD, FAAN, FASCO, the lead author of the NRG-BN007 manuscript as well as 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 Centre, and Attending Neurologist at, NewYork-Presbyterian.

NRG-BN007 accrued 159 eligible patients and stratified by recursive partitioning analysis class and intent to use Tumour Treating Fields.

Patients were randomised patients to either received ipilimumab and nivolumab or temozolomide (79 immunotherapy, 80 temozolomide).

With 95% power to detect a hazard ratio (HR) ≤ 0.58 for PFS at a one-sided significance level (p) of 0.15, superior PFS with immunotherapy in phase II would lead to phase III overall survival testing.

A pre-planned analysis of phase II data conducted after 100 centrally determined PFS events showed no significant PFS improvement for ipilimumab and nivolumab vs.

temozolomide (median 7.7 months vs.8.5 months, HR 1.47, 70% CI 1.19-1.83, 1-sided p=0.96; 95% CI 0.98-2.2).

Overall survival is immature (> 50% alive) but with no observed difference between arms (median ~13 months each, HR 0.95, 95% CI 0.61-1.49, p=0.36).

Since the trial did not show superior PFS in phase II, it will not be proceeding to assess overall survival in a phase III trial.

Source: NRG Oncology