Abstract
Abstract INTRODUCTION Approximately 30% of glioblastomas harbor the tumor specific EGFRvIII mutation. hEGFRvIII-CD3 bi-scFv (Brain Bi-Specific T Cell Engager - BRiTE) is a novel bispecific antibody construct which can redirect a patient’s entire repertoire of T cells (TCR-agnostic) to specifically lyse EGFRvIII-positive tumor cells. Compared to CAR-T therapy, it offers a highly potent yet off-the-shelf approach for glioblastoma. BRiTE is now entering Phase I clinical trials (NCT04903795) and will be trialed as a monotherapy or with autologous T cell infusion. Migration of T cell binding macromolecules across the blood-brain barrier may be facilitated by activated T cells which adhere to the microvascular endothelium and enter the brain parenchyma. Concurrent administration of activated T cells could therefore enhance trafficking of BRiTE and other antibody-based macromolecules into the intracerebral compartment. HYPOTHESIS We hypothesize that treatment of EGFRvIII-positive WHO grade IV malignant glioma with BRiTE alone or with peripheral T-cell infusion is safe and can induce objective tumor shrinkage at tolerable doses. TRIAL DESIGN/OBJECTIVES A maximum of 18 patients with newly diagnosed or recurrent WHO grade IV malignant EGFRvIII+ glioma will be enrolled after undergoing standard of care treatment. The primary objective will be evaluating the safety of BRiTE alone and with autologous T cell infusion. Patients will receive a single BRiTE infusion, followed 14 days later by an infusion of activated autologous T cells and a second bolus BRiTE infusion. Dose escalation and de-escalation will be managed using a Bayesian optimal interval design. Secondary objectives will be to describe clinical benefit as determined by objective response rate per mRANO criteria, and to evaluate BRiTE pharmacokinetics in serum. CONCLUSION We describe a first-in-human trial of bispecific T cell engager therapy for glioblastoma. We also describe our novel approach for enhancing intracranial penetration of BRiTE using autologous T cell infusion.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.