New Antibody Therapy Shows Activity in Patients With Medulloblastoma

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Effective and safe treatments are needed for medulloblastoma—the most common type of cancerous brain tumor in children—especially for patients whose cancer has spread to the spinal cord. A recent phase I clinical trial has generated promising results for a new blocking antibody therapy that targets a protein critical to medulloblastoma cells’ ability to multiply and spread. These findings were published by Saulnier Sholler et al in Clinical Cancer Research.


The antibody, called TB-403, recognizes placental growth factor (PlGF), which is overexpressed in some types of malignant tumors. The research team previously showed that PlGF and its receptor neuropilin 1 (NRP1) are often overexpressed in human medulloblastomas and are required for its growth and progression in experimental models in mice. That work also demonstrated that blocking the PlGF/NRP1 pathway in medulloblastoma models caused tumor regression, decreased spread to the spinal cord, and prolonged survival.

“Beyond the new biological insights, the experimental results were particularly exciting because blocking PlGF, unlike other cancer-related pathways, was safe in humans and thus was a particularly promising strategy in the pediatric population,” said senior study author Rakesh K. Jain, PhD, Director of the E.L. Steele Laboratories for Tumor Biology at Massachusetts General Hospital and the Andrew Werk Cook Professor of Radiation Oncology at Harvard Medical School. “We are thrilled to see the initial translation of these concepts into a clinical trial.”

Trial Methodology and Findings

The investigators’ phase I, open-label, multicenter dose-escalation study enrolled 15 children with relapsed or refractory medulloblastoma that did not respond to standard treatments. Patients received increasing doses of the anti-human PlGF antibody TB-403 (20 mg/kg, 50 mg/kg, 100 mg/kg, and 175 mg/kg), and all patients received two doses of TB-403 in the first cycle of treatment. The maximum tolerated dose was not reached. Moreover, although there were no partial tumor responses in this treatment-refractory population, 7 of 11 patients experienced disease stabilization, which persisted for more than 100 days in 4 of those patients.

The investigators concluded that TB403 treatment was well tolerated and induced stable disease in some patients with medulloblastoma in a setting with no effective treatments available.

“These findings indicate that treatment with TB-403 should be tested in larger studies of children with advanced medulloblastoma and perhaps at earlier stages, in combination with standard therapies,” says lead and corresponding author Giselle L. Saulnier Sholler, MD, Director of the Isabella Santos Foundation Solid and Rare Tumor Program and Chair of the Beat Childhood Cancer Research Consortium at Levine Children’s Hospital.

Disclosure: The clinical study was supported by Oncurious NV and the Beat Childhood Cancer Foundation. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.