Dr. Souweidane Presents DIPG Trial Update at ASCO 2019

Mark Souweidane, MD, director of pediatric neurosurgery at Weill Cornell Medicine Brain and Spine Center and co-director of the Weill Cornell Medicine Children’s Brain Tumor Project, presented an update to his clinical trial for DIPG at the 2019 meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Dr. Souweidane, along with his colleagues at Memorial Sloan Kettering Cancer Center, where the infusions took place, updated the results of the landmark trial testing convection-enhanced delivery (CED) of a drug directly to the site of the deadly brain stem tumor.

The presentation included a dose-response assessment detailing volume and distribution of the drug 124I-8H9 (Omburtamab) in 37 children, and showing an increase in overall survival time to a median 27.2 months, with a range from 11.5 months to 72.4 months (more than six years, for a disease that rarely sees more than a one-year survival time). In children, of course, survival times need to be measured in decades, not months, to be successful, but any approach that shows a survival advantage for this fatal tumor is exciting news.

In addition to Dr. Souweidane, the authors included Kim Kramer, Neeta Pandit-Taskar, Zhiping Zhou, Pat Zanzonico, Maria Donzelli, Serge K. Lyashchenko, Sofia Haque, Sunitha B Thakur, Nai-Kong V. Cheung, Steven M. Larson, and Ira J. Dunkel of Memorial Sloan Kettering Cancer Center, New York, NY; and Weill Cornell Medicine, New York.

The complete abstract follows:



Diffuse intrinsic pontine glioma (DIPG) represents one of the most deadly central nervous system tumors of childhood with a median survival of less than 12 months. Convection-enhanced delivery (CED) has been recently hypothesized as a means for efficiently distributing therapeutic agents within the brain stem. We conducted this study to evaluate CED in children with DIPG.

We performed a standard 3+3 phase I, open-label, dose escalation study in patients with non-progressive DIPG 4 to 14 weeks post-completion of radiation therapy. Seven dose levels of a single injection of 124I-8H9 (Omburtamab) (Y-mAbs Therapeutics, USA) (range 0.25 to 4.0 m Ci, 250 to 4,000 mcl) were studied.

Results: 37 children were treated with 34 evaluable for primary and secondary endpoints. The median age at enrollment was 6.8 years old (range 3.2-17.9). There was no dose limiting toxicity (DLT). Among adverse events that were at least possibly related to the treatment there were no grade 4 or 5 events, and only 4 grade 3 events in 4 patients (2 hemiparesis, 1 skin infection and 1 anxiety), all of which were reversible. Estimations of distribution volumes based on T2-weighted imaging were dose dependent and ranged from 1.5 to 20.8 cm3, and for dose level 7, 10.5-19.0 cm3. The mean volume of distribution/volume of infusion ratio (Vd/Vi) was 3.4±1.1, and for dose level 7,3.5 ± 1.0. The mean lesion absorbed dose was 33.3 ±25.9 Gy, and for dose level 7, 50.1±22.9 Gy. The mean ratio of lesion-to-whole body absorbed dose was 910.The mean volume of distribution/tumor volume ratio on dose level 7 was 82.5%, but the mean tumor overlap was 40.5%. No death occurred as a result of the treatment. Median survival was15.3 months (n = 29, 95% CI 12.7-17.4). Median follow-up time of the 5 surviving patients is 27.2 months (range 11.5-72.4). Overall survival rate at 12 months (OS12) was 64.7% (22/34, 4 alive), and overall survival rate at 24 months (OS24) 14.7% (5/34, 3 alive).

CED in the brain stem of children with DIPG who were previously irradiated is a safe therapeutic strategy. An infusion volume of 4,000 mcl appears to be a reasonable single dose for a target distribution volume but enhanced tumor coverage is likely needed.

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