A clinical trial evaluating dual immunotherapy before brain surgery lengthened survival in patients with recurrent glioblastoma, according to findings published in Nature Communications. The surgical window-of-opportunity study, designated NCT04606316, assessed whether combining nivolumab and ipilimumab altered immune activity and patient outcomes compared to single-agent treatment or surgery alone.
Investigators screened 71 patients between 2021 and 2024, randomizing 63 into an intention-to-treat cohort and treating 58. Researchers assigned participants to one of three arms: Arm 1 received pre-surgical nivolumab and ipilimumab, Arm 2 received nivolumab alone, and Arm 3 received a placebo before surgery. After resection, patients in Arms 1 and 3 received dual checkpoint blockade, while Arm 2 continued on nivolumab monotherapy until tumor progression or unacceptable toxicity.
The trial met its primary endpoint for Arm 1, demonstrating that neoadjuvant dual therapy significantly boosted tumor-infiltrating lymphocyte density compared with the untreated control group. Secondary endpoints tracked overall survival. Patients receiving the dual regimen in Arms 1 and 3 reached a median overall survival of 402 days with a 95% confidence interval of 265 to 571 days, compared to 273 days with a 95% confidence interval of 166 to 506 days for those on nivolumab alone.
Exploratory testing revealed that dual blockade triggered intratumoral immune activation and raised interferon-related gene expression in blood samples. Improved survival tracked with higher lymphocyte density and early interferon-signature responses, but did not correlate with tumor mutational burden. Doctors recorded no unanticipated toxicities during the trial.
Bristol Myers Squibb supplied both medications for the research but held no role in the trial design, data collection, analysis, or manuscript writing. Study leaders Timothy F. Cloughesy, Robert M. Prins, and Patrick Y. Wen jointly directed the research across institutions including the University of California Los Angeles, Dana-Farber Cancer Institute, and Memorial Sloan Kettering Cancer Center, with funding from the National Cancer Institute, the Parker Institute for Cancer Immunotherapy, and nonprofit brain tumor foundations.
