MTX110, an investigational water-soluble formulation of panobinostat, is showing promising results in patients with recurrent glioblastoma. Data from the phase 1 MAGIC-1 study (NCT05324501) indicates potential improvements in overall survival (OS) and progression-free survival (PFS) when MTX110 is administered via convection-enhanced delivery. This approach aims to overcome the challenges of delivering effective drug concentrations to brain tumors.
Efficacy in Recurrent Glioblastoma
The phase 1 MAGIC-1 study evaluated the feasibility, safety, and efficacy of MTX110 in recurrent glioblastoma patients. In cohort A, early data showed that two patients had an OS of 12 and 13 months, respectively. Follow-up is ongoing for the remaining two patients in this cohort. Patient 3 experienced a PFS of 6 months and an OS of 13 months. Patient 4 had not experienced disease progression, with both PFS and OS at 12 months to date.
MTX110: Overcoming the Blood-Brain Barrier
MTX110 is designed as a water-soluble form of panobinostat, complexed with hydroxypropyl-β-cyclodextrin to facilitate convection-enhanced delivery directly to brain tumors. The standard oral formulation of panobinostat (Farydak) is not typically used for brain cancers due to its limited ability to penetrate the blood-brain barrier, resulting in inadequate drug concentrations in the brain. MTX110, delivered via a catheter system, aims to bypass this barrier, potentially exposing tumors to higher drug concentrations while minimizing systemic exposure and toxicity.
MAGIC-1 Trial Design
The MAGIC-1 trial is a phase 1 study assessing MTX110 in patients with recurrent glioblastoma. Cohort A receives weekly doses of MTX110 via convection-enhanced delivery until unacceptable toxicity or disease progression. Cohort B receives the same dose with the option to reposition the catheter upon disease progression, continuing weekly dosing until toxicity or progression. The primary endpoints are safety and determining the recommended phase 2 dose. Secondary endpoints include OS, PFS, and best overall response rate.
Eligible patients are 18 years or older with recurrent glioblastoma, able to tolerate surgery and general anesthesia, and have a life expectancy of over 3 months. Patients undergoing re-irradiation, with a history of carmustine wafers, or with contraindications for MRI are excluded. The study also excludes patients with brainstem, cerebellum, or spinal cord lesions, or posterior fossa tumors.
Prior Data in Diffuse Midline Glioma
These findings build upon earlier data from a phase 1 study (NCT04264143) of MTX110 in diffuse midline glioma, presented at the 21st International Symposium on Paediatric Neuro-Oncology (ISPNO 2024). In this study, 9 patients with diffuse midline glioma treated with MTX110 achieved a median OS of 16.5 months. MTX110 was generally well-tolerated in this patient population.
