First-in-Child Brain Tumor Trial Led by Children’s Healthcare of Atlanta Shows Anti-Tumor Responses

ATLANTA (December 16, 2025) - Researchers at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta conducted a first-in-child, Phase I clinical trial in recurring malignant brain tumor patients to test a treatment inhibiting STAT3, a cancer stem cell protein which regulates brain tumors in children. Led by pediatric oncologist Tobey MacDonald, MD, who discovered STAT3 is critical to certain childhood brain tumors, the results were recently published in the Journal of Clinical Investigation Insight and showed the therapy, known as WP1066, induces anti-tumor immune responses.

"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 who is also a professor of pediatrics at Emory University School of Medicine.

While the preclinical efficacy of WP1066 had been previously demonstrated, and its effectiveness had been studied among adults, this trial was the first to test it in children. Dr. MacDonald and his team recruited pediatric patients with high-grade glioma, which include diffuse midline glioma (DMG) and DIPG, and account for most pediatric brain tumor-related deaths. Both DMG and DIPG have an average survival rate of nine to 11 months following diagnosis. Additionally, patients with relapsed medulloblastoma and ependymoma who have no accepted standard therapy following a relapse were also included in the study. Thus, Dr. MacDonald's research helps fill a critical need to identify new treatment options for patients with these incurable tumors.

During the trial, 10 children were treated with WP1066 twice daily for 14 days to determine the maximum feasible dose. Compassionate use treatment in three children with high-grade glioma was also evaluated. Results showed there was no significant toxicity, and a maximum feasible dose was determined. Importantly, WP1066 suppressed the expression of STAT3, inhibiting its activity and demonstrating 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 of this study are the foundation of the Phase II concept Dr. MacDonald's team would like to pursue in a follow-up trial. The current study was funded by Peach Bowl LegACy Fund and CURE Childhood Cancer. WP1066 inhibits STAT3, a cancer stem cell protein that regulates gene activity critical for cancer cell survival while simultaneously activating the immune response against the cancer cells.