Positive Phase 1 Results of MTX110 in DMG Brain Cancer Show Increased Survival at ISPNO 2024
On July 2, 2024, Biodexa Pharmaceuticals PLC shared promising results from a Phase 1 clinical study of MTX110 targeted at Diffuse Midline Glioma (DMG), a rare and aggressive pediatric brain cancer. The data was presented at the International Symposium on Pediatric Neuro-Oncology (ISPNO 2024) in Philadelphia.
Study Outcomes
The Phase 1 study showed that MTX110 treatment was generally well tolerated among patients. Only one Grade 4 adverse event was reported, which investigators determined was unrelated to the drug but linked to the infusion process and tumor location. Other adverse events, primarily associated with the infusion, were classified as Grade 2 or 3 in severity.
Despite the study’s limited power to demonstrate efficacy, the median progression-free survival (PFS) observed was 10 months, ranging from 8 to 20 months. The overall survival (OS) median for patients in the study was 16.5 months, with a range from 12 to 35 months. These outcomes compare favorably against a historical cohort median OS of 10 months.
Study Design
Conducted by Columbia University Irving Medical Center, the open-label study included patients recently diagnosed with DMG. MTX110 was administered via convection-enhanced delivery (CED) using a subcutaneous pump connected to a catheter implanted directly into the pons. The study followed a 3+3 dose-escalating design, involving two 48-hour infusions held seven days apart. Nine patients participated in the study across three dosage groups: 30 M (n=3), 60 M (n=4), and 90 M (n=2), with the latter being the optimal dose.
The primary goal was to evaluate both the safety and the maximum tolerated dose of MTX110, while secondary endpoints included Progression-Free Survival and Overall Survival.
Background on MTX110
MTX110 is a water-soluble form of panobinostat free base, which enables its delivery in potentially therapeutic doses directly to the tumor site. Panobinostat is a histone deacetylase inhibitor that demonstrated high potency against DMG tumor cells in both in vitro and in vivo models. In a pivotal study, it was identified as the most promising compound out of 83 anticancer agents tested in DMG cell lines.
Previous Studies
Previously, Biodexa shared headline results from another Phase I study conducted at the University of California, San Francisco (UCSF). The primary aim was to determine an appropriate dosage for a proposed Phase II study. This study included seven patients who had been newly diagnosed with DMG and had received radiation therapy four to 14 weeks prior to starting MTX110 treatment. The UCSF study administered MTX110 using CED and utilized MRI to guide and monitor drug distribution within the tumor. Patients could undergo up to 12 treatment cycles every four to eight weeks. The median overall survival in this study, based on Kaplan Meier analysis, was 26.06 months.
Mechanism of Action
MTX110’s formulation allows it to bypass the blood-brain barrier, delivering high concentrations of the drug directly to the tumor while minimizing systemic exposure and potential side effects. This targeted delivery system could represent a significant advancement in treating brain cancers that are otherwise difficult to manage due to poor drug penetration in the brain.
Conclusion
The Phase 1 study of MTX110 in DMG patients highlighted the drug’s potential to improve survival outcomes significantly compared to existing benchmarks. This development serves as a promising step forward in the treatment of one of the most challenging pediatric brain cancers, paving the way for further research and potential future application in clinical settings.
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