Background: Median survival in patients with diffuse intrinsic pontine glioma (DIPG) varies between 11 months for children and 20 months for adults. There is no standard of care treatment other than radiation therapy. This study aimed to determine the safety, tolerability, and distribution of nanoliposomal irinotecan (nal-IRI) delivered via CED in patients with DIPG.
Methods: Newly diagnosed DIPG patients > 2 years were eligible for enrollment. Dose level (DL) 1 and 2 were completed (DL1 = 2 mL of nal-IRI [20 mg/mL] DL2 = 3 mL of nal-IRI [20 mg/mL]). Nal-IRI was co-infused with gadoteridol via CED to achieve maximal tumor coverage. The distribution of infusate mixture was monitored with real-time magnetic resonance imaging (MRI). The study employed an accelerated dose escalation approach and transitioned to a conventional 3 + 3 design based on predefined rules. The study was terminated prematurely due to the discontinuation of drug supply by industry partner.
Results: Six patients (median age 10 years, range 5-40) underwent a total of 13 treatments (median 2, range 1-5/patient). Four grade 3 adverse events, (muscle weakness n = 2, dysarthria n = 1, and gait disturbance n = 1) were observed, including one dose-limiting toxicity (muscle weakness). Mean tumor volume prior to the first CED treatment was 28.9 ± 8.8 cm3 with a mean tumor coverage per treatment of 35.3% ± 17.6. Twelve-month overall survival (OS) was 67% (95% CI 38-100).
Conclusions: Repeated CED of nal-IRI in patients with DIPG demonstrated an acceptable risk profile with reasonable tumor coverage. Additional investigations utilizing this strategy should be evaluated in a larger patient cohort to determine efficacy.
Keywords: DIPG; convection-enhanced delivery; nano liposomal irinotecan.
© The Author(s) 2025. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.