Abstract
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.
Highlights
OS2966 is a first-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin
Summary of Potential Risks and Benefits. Given this is a Phase 1 trial, patients may not derive any benefit from study treatment; it is possible that patients with recurrent/progressive high-grade gliomas (HGG) may experience stable disease or partial or complete response, which may lead to longer PFS, as a result of treatment with OS2966
OS2966 has been studied in four nonclinical, nonhuman primate (NHP) studies
Summary
OS2966 is a first-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. We present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. High-grade gliomas (HGGs) continue to be among the most formidable cancer diagnoses and highlight the unmet need for effective treatments. They include WHO Grade III gliomas (anaplastic astrocytoma, anaplastic oligodendroglioma, and malignant glioma) as well as Grade IV (glioblastoma). They are the most common and most malignant primary brain tumors and are associated with high morbidity and mortality [1]. Despite standard of care therapy (which includes maximal surgical resection, radiotherapy, and chemotherapy), most of these tumors recur within 6 to 9 months and the median overall survival remains at 15 months [2].
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