A Phase I clinical trial demonstrated that a targeted approach to treating a deadly brain tumor in children called diffuse intrinsic pontine glioma (DIPG) is safe, reported Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center investigators. This is the first larger scale study using a radiation-based direct drug delivery approach to treat and image DIPG.
DIPG is an aggressive cancer without any effective treatment—fewer than 10% of children survive two years after diagnosis. The tumor embeds itself into the brainstem that regulates vital functions, including breathing, heart rate and muscle control. Neither chemotherapy drugs nor surgery can reach the tricky location at the base of the brain.
The new study, published Feb. 19 in Neuro-Oncology, established that infusing a drug called 124I-Omburtamab directly into the brainstem is a safe way to maximize delivery of the drug right where DIPG tumors develop—without poisoning the rest of the body.
We've shown we can deliver the drug, and we can do it safely. Now we can start laying the groundwork for modification, tailoring, redosing and scheduling."
Dr. Mark Souweidane, study lead, professor of neurological surgery in pediatrics and a pediatric neurosurgeon at NewYork-Presbyterian/Weill Cornell Medical Center and Memorial Sloan Kettering Cancer Center
Direct delivery
As the name implies, DIPG tumors are not clearly contained in a separate mass but diffuse through and infiltrate surrounding healthy tissue, making treatment difficult.
Dr. Souweidane and his team used a recently approved technique called convection enhanced delivery (CED) to inject a drug directly into the tumor region. CED involves using a syringe attached to a long, thin tube inserted into a patient's brain. Gentle pressure on the syringe delivers medication through the tube to a targeted brain region. Testing the technique in preclinical models, showed that the brainstem could be targeted accurately and the fluid volume injected into the brain could be tolerated without injury. "That opened up an amazing opportunity and hope that we could do this," he said.
After testing many classes of therapeutic agents, the researchers chose 124I-Omburtamab, a radio-labeled monoclonal antibody that binds to a protein that's overexpressed on the tumor cells. The antibody finds the tumor cells and delivers a dose of radiation that kills them. At the same time, the drug can be visualized in Positron Emission Tomography (PET) scan images, showing how much drug is delivered in the brain, how quickly it gets there and its precise location. The body eventually clears the radiation within a few weeks.
Ready for the next phase
In 2018, Dr. Souweidane published an initial study in The Lancet Oncology with 28 children receiving CED treatment for DIPG. This new study is a Phase I clinical trial with 50 patients to assess safety and determine the best drug dosages to treat DIPG. They used CED to slowly infuse 124I-Omburtamab over 12 hours into the brains of patients and conducted PET scans before and after infusions.
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"We showed reproducibly that our approach increased the therapeutic concentration at the tumor site nearly 1,000-fold greater than throughout the body," said Dr. Souweidane, who is also director of pediatric neurological surgery. "We're essentially eliminating any concern about systemic toxicity, which usually limits the dose we can administer."
The team determined that the maximum tolerated activity of the drug was 6 millicuries, which is the about the exposure of a standard thyroid scan using radioactive iodine. They also found that patients could tolerate up to 8 milliliters, a little over a teaspoon, of the drug safely. There were no clinically significant, procedure-related complications or deaths. However, the researchers note that the infusion location and patient's pre-operative symptoms likely play a significant role in drug tolerance.
"For someone like me who's been in this field for about 40 years, 'survival' is not a word we use with this disease—these findings offer a glimmer of hope where there was none," Dr. Souweidane said. "There are three long-term survivors. One is approaching four years, one is about seven years and another one is almost 11 years from diagnoses." Although this trial wasn't assessing efficacy, about 18% of the patients lived for two years after diagnosis.
The next step is a Phase I/II clinical trial to test a new form of the drug and to methodically evaluate how effective this treatment is for a larger group of DIPG patients. "I'm enthusiastic, and we're jumping in headfirst," Dr. Souweidane said.
Weill Cornell Medicine
Journal reference:
Souweidane, M. M., et al. (2025). Phase 1 dose-escalation trial using convection-enhanced delivery (CED) of radio-immunotheranostic 124I-Omburtamab for diffuse intrinsic pontine glioma (DIPG). Neuro-Oncology. doi.org/10.1093/neuonc/noaf039.