Researchers at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta have conducted a first-in-child, Phase I clinical trial for children with recurring malignant brain tumors. The trial tested WP1066, a treatment designed to inhibit STAT3, a protein that plays a key role in regulating certain pediatric brain tumors.
The study was led by Dr. Tobey MacDonald, a pediatric oncologist who also serves as a professor of pediatrics at Emory University School of Medicine. Dr. MacDonald discovered the importance of STAT3 in childhood brain tumors and directed the research team in evaluating WP1066’s effectiveness among young patients.
“The results of this first-in-child trial show some encouraging signals of activity, such as partial tumor response in a diffuse intrinsic pontine glioma (DIPG) patient and clear anti-tumor immune changes,” said Dr. MacDonald.
While earlier studies had demonstrated WP1066’s efficacy in preclinical settings and among adults, this is the first time it has been tested on children. The clinical trial enrolled pediatric patients diagnosed with high-grade glioma—including diffuse midline glioma (DMG) and DIPG—which are responsible for most deaths related to pediatric brain tumors. Both DMG and DIPG typically have an average survival rate of nine to eleven months after diagnosis. The study also included patients with relapsed medulloblastoma and ependymoma who lack established treatment options after relapse.
Ten children received WP1066 twice daily over 14 days to establish the maximum feasible dose. Three additional children with high-grade glioma were treated under compassionate use protocols. According to the findings, there was no significant toxicity observed, and researchers determined the maximum feasible dose for future studies. The drug was found to suppress STAT3 expression, inhibiting its activity and triggering anti-tumor immune responses.
“We also reported the drug activity in a compassionate use case suggesting it may work better after radiation for newly diagnosed malignant glioma patients,” said Dr. MacDonald.
The results from this study will inform a planned Phase II trial by Dr. MacDonald’s team. Funding for the current research came from Peach Bowl LegACy Fund and CURE Childhood Cancer.
WP1066 targets STAT3—a protein essential for cancer cell survival—and simultaneously stimulates an immune response against cancer cells.
