NRG Oncology recently reported the results of the National Cancer Institute sponsored phase II/III NRG-BN007 clinical trial (https://clinicaltrials.gov/study/NCT04396860) 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 (https://doi.org/10.1200/JCO-25-00618).
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 Tumor Treating Fields. Additionally, tumors 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 Center, and Attending Neurologist at, NewYork-Presbyterian.
NRG-BN007 accrued 159 eligible patients and stratified by recursive partitioning analysis class and intent to use Tumor Treating Fields. Patients were randomized 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.
Funding
This project was directly supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), and U24CA196067 (NRG Specimen Bank) from the National Cancer Institute (NCI), National Institutes of Health. The study is sponsored by the NCI and is led and conducted by the NCI-funded NRG Oncology with participation from the NCI-funded National Clinical Trials Network. Bristol Myers Squibb provided support to the study through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program. Andrew B. Lassman was supported in part by The William Rhodes and Louise Tilzer-Rhodes Center for Glioblastoma at New York-Presbyterian, The Michael Weiner Glioblastoma Research Into Treatment Fund, the Hearst Foundations, and NIH/NCI/NCATS P30CA013696, UG1CA189960, and 5UL1TR001873.
Citation
Lassman AB, Polley MC, Iwamoto FM, Sloan AE, Wang TJC, Aldape KD, Wefel JS, Gondi V, Gutierrez AN, Manasawala MH, Gilbert MR, Sulman EP, Wolchok JD, Green RM, Neil EC, Lukas RV, Goldlust SA, Snuderl M, Galbraith K, Dignam JJ, Won M, Mehta MP. Dual Immune Check Point Blockade in MGMT-Unmethylated Newly Diagnosed Glioblastoma: NRG Oncology BN007, a Randomized Phase II/III Clinical Trial. J Clin Oncol. 2025 Aug 8:JCO2500618. doi: 10.1200/JCO-25-00618. Epub ahead of print. PMID: 40779733.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.
Journal
Journal of Clinical Oncology