Duke researchers are leading a phase I clinical trial to evaluate a new experimental treatment for glioblastoma, one of the most aggressive and deadly forms of brain cancer.
The drug is a type of immunotherapy known as a Brain Bispecific T-cell Engager (BRiTE), which is designed to cross the blood-brain barrier and to help the patient’s own immune cells (T-cells) recognize and attack cancer cells.
Duke researchers developed EGFRvIII-BRiTE, which links the patient’s T cells to glioblastoma cells that express a specific protein found on aggressive brain tumors (Epidermal Growth Factor Receptor variant III). The trial is being conducted in collaboration with Adaptin Bio, Inc, a biotechnology company that develops precision cancer therapies.
The therapy has been in development at Duke’s Preston Robert Tisch Brain Tumor Center for the last decade. “This first-in-human study is an important step in determining whether this approach can translate into meaningful benefit for patients,” said Mustafa Khasraw, MD, professor of neurosurgery and principal investigator of the trial.
“Glioblastoma is a disease with a significant unmet clinical need, limited therapeutic options, and little improvement in outcomes,” Khasraw said. Patients diagnosed with glioblastoma typically survive only 12 to 18 months, and just 5% live longer than five years. Recurrence is common despite surgery, radiation therapy, and chemotherapy.
In preclinical studies, EGFRvIII-BRiTE (also called APTN-101) showed activity at very low doses. Because EGFRvIII is present only on tumor cells, it is designed to attack the cancer while sparing surrounding healthy cells. In aggressive disease models, the drug accurately targeted cancer cells and eliminated tumors.
Patients are now being enrolled in the clinical trial, in which the therapy will be administered to participants as a continuous infusion for four days, which will be repeated for as many as two additional infusions in 28-day cycles. Research and nursing teams will be monitoring patients closely and working to establish appropriate dosing amounts that could be used in larger follow-up studies.
Development is also under way on newer BRiTE formats that can be produced rapidly and at scale using the same immunotherapy platform. "Instead of creating customized treatments for each participant like CAR-T therapies, we can manufacture different BRiTEs in large quantities, making them potentially more accessible while maintaining precision and potency," said Kirit Singh, MD, PhD, who led the multidisciplinary team that finalized the drug for clinical trials.