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Open AccessArticle

Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging

1
Emory University School of Medicine, Atlanta, GA 30322, USA
2
Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA
3
OncoSynergy, Inc., Stamford, CT 06902, USA
4
H.Lee Moffitt Cancer Center and Research Institute, Departments of Neurosurgery and Neuro-Oncology, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2021, 13(1), 40; https://doi.org/10.3390/pharmaceutics13010040
Received: 1 December 2020 / Revised: 22 December 2020 / Accepted: 25 December 2020 / Published: 30 December 2020
(This article belongs to the Special Issue Drug Delivery to Brain Tumors)
Introduction: OS2966 is a first-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 the intratumoral, convection-enhanced delivery (CED) of OS2966. Gadolinium contrast will be added to OS2966 before each infusion, enabling the real-time visualization of therapeutic distribution via MRI. 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. View Full-Text
Keywords: glioblastoma; high-grade glioma; convection enhanced delivery; OS2966; CD29; β1 integrin; ITGB1; monoclonal antibody; clinical trial glioblastoma; high-grade glioma; convection enhanced delivery; OS2966; CD29; β1 integrin; ITGB1; monoclonal antibody; clinical trial
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MDPI and ACS Style

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. https://doi.org/10.3390/pharmaceutics13010040

AMA Style

Nwagwu CD, Immidisetti AV, Bukanowska G, Vogelbaum MA, 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(1):40. https://doi.org/10.3390/pharmaceutics13010040

Chicago/Turabian Style

Nwagwu, Chibueze D.; Immidisetti, Amanda V.; Bukanowska, Gabriela; Vogelbaum, Michael A.; Carbonell, Anne-Marie. 2021. "Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging" Pharmaceutics 13, no. 1: 40. https://doi.org/10.3390/pharmaceutics13010040

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