P17.03.A MAGIC-G1: A PHASE 1 DOSE-ESCALATION TRIAL OF WEEKLY INTRATUMORAL ADMINISTRATION OF THE SOLUBILISED FORMULATION OF PANOBINOSTAT (MTX110) IN PATIENTS WITH RECURRENT GLIOBLASTOMA (RGBM)

Abstract

Abstract BACKGROUND One of the biggest challenges in treating rGBM is achieving high local drug concentration. Convection enhanced delivery (CED) is a ‘direct-to-brain’ drug delivery method that previously demonstrated its usefulness in overcoming the blood-brain barrier, while also limiting systemic toxicity. MTX110 (Midatech Ltd), a water-soluble formulation of panobinostat, has demonstrated cytotoxic activity in GBM cell lines, as well as safety and efficacy in two pediatric diffuse pontine glioma trials. Delivery of MTX110 via an implanted pump and CED catheter system in patients with GBM appears to be an attractive treatment option, that allows for therapeutic doses of the drug to be delivered weekly directly to the tumor, thus avoiding systemic administration and therefore toxicity. MATERIAL AND METHODS Eligibility includes adult rGBM patients with a single enhancing lesion ≤3cm in maximal diameter; ≥4 weeks after chemotherapy, bevacizumab, or study drug; adequate organ function; and KPS ≥60%. MTX110 is continuously infused over 48hrs weekly at a rate of 0.5mL/h, via a CED catheter implanted into the enhancing disease recurrence connected to a fully internalized pump system. After safety of a single patient treated at 60μM has been established, 3-6 patients will be treated with MTX110 at 90μM as a single agent (Cohort 1). Patients in cohort 2 will receive MTX110 in combination with lomustine at a starting MTX110 dose of 60 μM and following the same dose-escalation approach. RESULTS As of March 30, 2023, the 1st patient was treated in monotherapy at 60μM and has received 12 weekly infusions of MTX110. No dose-limiting toxicities were observed. Observed study related adverse events (AEs) included: grade 1 cognitive disturbance, headache, and seizure; grade 2 candida wound infection, erythema of the scalp, bruising, and hemiparesis; and grade 3 abdominal seroma at pump insertion site. Enrolment is ongoing and the next patient will receive the 90 μM dose. CONCLUSION Weekly intratumoral administration of MTX110 via a fully internally implanted CED pump system is feasible. Updated results will be presented.