Convection-enhanced Delivery of OS2966 for Patients With High-grade Glioma Undergoing a Surgical Resection

Summary

Participation Requirements

Description

This study is an open-label, ascending-dose, 2-part study designed to determine the safety and tolerability of OS2966, as well as the optimal infusion parameters when administering OS2966 directly to the tumor and the surrounding tumor-infiltrated brain by CED in participants with recurrent/progress...

This study is an open-label, ascending-dose, 2-part study designed to determine the safety and tolerability of OS2966, as well as the optimal infusion parameters when administering OS2966 directly to the tumor and the surrounding tumor-infiltrated brain by CED in participants with recurrent/progressive HGG undergoing a surgical resection. OS2966 is an anti-CD29 (Beta1 Integrin) monoclonal antibody (mAb) that has demonstrated preclinical efficacy in resistant/recurrent glioblastoma animal models. This study will recruit participants with recurrent/progressive high-grade glioma (HGG; WHO Grade III or IV glioma). The development of effective treatments for HGG has been limited by an infiltrative growth pattern, the blood brain barrier (BBB), and the rapid development of therapeutic resistance. Convection-enhanced delivery is a specific technique that allows direct delivery of therapeutics to the brain and to brain tumors. Convection-enhanced delivery bypasses the BBB and allows for infusion of therapeutics that would otherwise be excluded from the central nervous system. Importantly, CEDs targeted delivery obviates systemic toxicity. OS2966 will be delivered by CED using the Infuseon Cleveland Multiport Catheter (ICMC) in both parts of the study. The ICMC is a type of catheter developed specifically for direct delivery of therapies to the brain. Participants enrolled in this study will undergo 2 staged parts of treatment. In Study Part 1, participants will receive a single intratumoral infusion of OS2966 directly to the contrast-enhancing bulk tumor by CED using one ICMC over 4 hours or until maximal tumor coverage is obtained. In Study Part 2, participants will undergo surgical resection of the previously infused tumor. Immediately following surgical resection, 2 ICMCs will be placed directly into the surrounding tumor-infiltrated brain, and OS2966 will be infused over a 4 hour period and then the catheters removed. To confirm the quality of OS2966 delivery, a gadolinium contrast agent will be added to OS2966 before each infusion in order to monitor the infusion via magnetic resonance imaging. All participants will be closely monitored clinically, and through the use of imaging assessments to determine how effective OS2966 is at preventing further disease progression. Tumor tissue will be collected in both study parts to evaluate how well OS2966 binds to its intended target and to confirm mechanism of action. All enrolled patients will also receive standard supportive care therapy.

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