ACTR-55. OPTIMIZED TREAT-RESECT-TREAT STUDY DESIGN FOR CONVECTION-ENHANCED DELIVERY OF A FIRST-IN-CLASS BIOLOGIC IN THE TREATMENT OF GLIOBLASTOMA

Abstract

INTRODUCTION: Development of effective treatments for high-grade glioma (HGG) including glioblastoma is hampered by 1) the blood brain barrier, 2) an infiltrative growth pattern, 3) rapid development of adaptive therapeutic resistance, and 4) dose-limiting toxicity due to systemic exposure. Novel therapeutics and delivery techniques are warranted to overcome these obstacles and meaningfully improve patient outcomes. OS2966 is the first ever clinical-ready therapeutic candidate against the adhesion receptor subunit, CD29/β1 integrin. CD29 is highly overexpressed in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy including immunotherapies. Here, we present a novel phase I trial design addressing all four obstacles plaguing effective treatment of HGG, while also enabling biomarker development. STUDY DESIGN: This 2-part, ascending concentration, phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinicallyindicated resection. In part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which is used for intratumoral convection-enhanced delivery (CED) of OS2966. Subsequently, patients 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) two-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active.