Biodexa Pharmaceuticals PLC announced data from a Phase 1 study of MTX110 in Diffuse Midline Glioma (DMG) f/k/a Diffuse Intrinsic Pontine Glioma, or DIPG, an orphan pediatric brain cancer were presented over the weekend at the 21st International Symposium on Pediatric Neuro-Oncology (ISPNO 2024) in Philadelphia, PA. Results of the Phase 1 study: Overall, the treatment was well tolerated by patients. There was one Grade 4 adverse event assessed by the investigators as unrelated to the drug but related to the infusion and tumor anatomy.

Most other adverse events were related to infusion and were deemed Grade 2 to 3. Although the study was not powered to reliably demonstrate efficacy, median progression free survival (PFS) was 10 months (range 8 to 20 months) and overall survival (OS) of patients in the study was 16.5 months (range 12 to 35 months). This compares favorably with median OS in a cohort of 316 cases of 10.0 months (Jansen et al, 2015. Neuro-Oncology 17(1):160-166).

Design of the Phase 1 study: The open label investigator-initiated study was conducted by Columbia University Irving Medical Center in patients newly diagnosed with DMG. Patients were administered MTX110 via convection enhanced delivery (?CED?) using a subcutaneous pump connected to a catheter directly implanted into the pons in a 3+3 dose-escalating design (NCT 04264143). As this was the first ever study of repeated infusions to the pons via an implanted CED catheter, the primary endpoint of the study was to evaluate the safety and maximum tolerated dose with secondary endpoints of Progression Free Survival and Overall Survival.

The number of infusions was limited to two, each of 48 hours, seven days apart. Nine patients were treated in the study (30 M group, n=3; 60 M group, n=4; 90 M group (optimal dose), n=2). Although the study was not powered to reliably demonstrate efficacy, median overall survival (OS) of patients in the study was 16.5 months.

This compares favorably with median survival rate in a cohort of 316 cases of 10.0 months (Jansen et al, 2015. Neuro-Oncology 17(1):160-166). MTX110 in DMG: In October 2020, the Company announced headline results from a Phase I study at the University of California, San Francisco (?UCSF?) in patients with DMG (the ?UCSF study?

NCT03566199). The primary endpoint of the study was to determine the dosage regimen to be used in a proposed Phase II study of the safety and efficacy of MTX110 in patients with DIPG. Preliminary high-level data from the UCSF study supports a dose of between 60µM and 90µM of MTX110, depending upon patient tolerance over the course of 12 infusions in Phase II.

In total, seven patients were recruited into the UCSF study. Patients were newly diagnosed with DMG and received focal external beam radiation therapy four to 14 weeks before commencement of MTX110 treatment. MTX110 was administered directly into the tumour via a micro-catheter using CED with gadolinium-enhanced intra-operative MRI to guide and track drug distribution to the tumour.

Patients could receive up to 12 cycles of treatment every four to eight weeks. The dose was escalated between and within patients as tolerated initially by increasing the infusion volume at a concentration of 30µM MTX110 and then with higher drug concentrations of 60µM and 90µM as the sixth and seventh dose increments, respectively. Median overall survival based on Kaplan Meier analysis was 26.06 months.

Survival was not an endpoint of the UCSF study nor was the study powered for statistical significance.