Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging
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...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/1/40 |
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| author | Chibueze D. Nwagwu Amanda V. Immidisetti Gabriela Bukanowska Michael A. Vogelbaum Anne-Marie Carbonell |
| author_facet | Chibueze D. Nwagwu Amanda V. Immidisetti Gabriela Bukanowska Michael A. Vogelbaum Anne-Marie Carbonell |
| author_sort | Chibueze D. Nwagwu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T13:41:06Z |
| format | Article |
| id | doaj.art-e2d3dad5df424c85b592867ceed5d7ce |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T13:41:06Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e2d3dad5df424c85b592867ceed5d7ce2023-11-21T03:06:13ZengMDPI AGPharmaceutics1999-49232020-12-011314010.3390/pharmaceutics13010040Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time ImagingChibueze D. Nwagwu0Amanda V. Immidisetti1Gabriela Bukanowska2Michael A. Vogelbaum3Anne-Marie Carbonell4Emory University School of Medicine, Atlanta, GA 30322, USARutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USAOncoSynergy, Inc., Stamford, CT 06902, USAH.Lee Moffitt Cancer Center and Research Institute, Departments of Neurosurgery and Neuro-Oncology, Tampa, FL 33612, USAOncoSynergy, Inc., Stamford, CT 06902, USAIntroduction: 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.https://www.mdpi.com/1999-4923/13/1/40glioblastomahigh-grade gliomaconvection enhanced deliveryOS2966CD29β1 integrin |
| spellingShingle | Chibueze D. Nwagwu Amanda V. Immidisetti Gabriela Bukanowska Michael A. Vogelbaum Anne-Marie Carbonell Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging Pharmaceutics glioblastoma high-grade glioma convection enhanced delivery OS2966 CD29 β1 integrin |
| title | Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging |
| title_full | Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging |
| title_fullStr | Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging |
| title_full_unstemmed | Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging |
| title_short | Convection-Enhanced Delivery of a First-in-Class Anti-β1 Integrin Antibody for the Treatment of High-Grade Glioma Utilizing Real-Time Imaging |
| title_sort | convection enhanced delivery of a first in class anti β1 integrin antibody for the treatment of high grade glioma utilizing real time imaging |
| topic | glioblastoma high-grade glioma convection enhanced delivery OS2966 CD29 β1 integrin |
| url | https://www.mdpi.com/1999-4923/13/1/40 |
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