Working Paper Article Version 1 This version is not peer-reviewed

Clinical Development of an Anti- β1 Integrin Antibody for the Treatment of High-Grade Glioma via Convection Enhanced Delivery

Version 1 : Received: 1 December 2020 / Approved: 2 December 2020 / Online: 2 December 2020 (09:11:37 CET)

A peer-reviewed article of this Preprint also exists.

Nwagwu, C.D.; Immidisetti, A.V.; Bukanowska, G.; Vogelbaum, M.A.; Carbonell, A.-M. Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging. Pharmaceutics 2021, 13, 40. Nwagwu, C.D.; Immidisetti, A.V.; Bukanowska, G.; Vogelbaum, M.A.; Carbonell, A.-M. Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging. Pharmaceutics 2021, 13, 40.

Journal reference: Pharmaceutics 2020, 13, 40
DOI: 10.3390/pharmaceutics13010040

Abstract

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Subject Areas

Glioblastom; high-grade glioma; convection enhanced delivery; OS2966; CD29; β1 integrin; ITGB1; monoclonal antibody; clinical trial

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