Phase 1 nivolumab plus focused ultrasound and microbubbles tests blood-brain barrier opening in recurrent pediatric brain tumors

This open-label Phase 1 study from Children’s National Research Institute tests neuronavigation-guided low-intensity focused ultrasound with sulfur hexafluoride microbubbles (Lumason, Bracco) to transiently open the blood-brain barrier alongside nivolumab, Bristol Myers Squibb’s PD-1-blocking antibody. One group includes children and young adults with relapsed or progressive brainstem diffuse midline glioma; another includes relapsed or progressive high-grade brain tumors requiring resection, allowing a preoperative ultrasound session and subsequent postoperative combination treatment.

The study evaluates safety and feasibility, drug-delivery biology, and exploratory antitumor and immune effects. Better CNS delivery is a hypothesis, not evidence that nivolumab will overcome the several barriers to immunotherapy in these tumors. Treatment options after progression depend on diagnosis: dordaviprone received FDA accelerated approval in August 2025 for patients aged 1 year or older with progressive H3 K27M-mutant diffuse midline glioma after prior therapy. That indication does not cover every tumor in this study. Re-irradiation, surgery when appropriate, and other clinical trials remain important considerations in the broader recurrent pediatric high-grade brain tumor population.