MAGIC-G1 Study Provides Updated Findings With MTX110 in Recurrent Glioblastoma

Updated progression-free survival (PFS) and overall survival (OS) data from the phase 1 MAGIC-G1 study (NCT05324501), which is examining MTX110 in patients with recurrent glioblastoma, have been released.¹

Findings from cohort A of the study, which completed recruitment of 4 patients in October 2023, showed that 2 patients died since initiating treatment with an OS of 12 and 13 months, respectively. Two other patients remain in post-study follow-up; patient 3 experienced a PFS of 6 months and an OS to date of 13 months, and patient 4 had not yet experienced confirmed disease progression, with a PFS and OS of 12 months to date.

MTX110 is a water-soluble formulation of panobinostat free base. The agent is manufactured via complexation with hydroxypropyl-β-cyclodextrin, which allows for convection-enhanced delivery at potentially chemotherapeutic doses directly to the tumor site. MTX110 is administered via a catheter system directly into and around the tumor to bypass the blood-brain barrier.

Panobinostat is a non-selective histone deacetylase inhibitor. The available oral formulation panobinostat lactate (Farydak) is not effective for the treatment of patients with brain cancers due to poor blood-brain barrier penetration and inadequate brain drug concentrations.

MAGIC-G1 is a 2-cohort, ascending-dose trial evaluating intra-tumoral MTX110 in adult patients with recurrent glioblastoma. Eligible patients need to be able to undergo surgery and general anesthesia, as well as have a life expectancy over 3 months.²

Patients in cohort A received weekly dosing of MTX110 by convection-enhanced delivery via a programmable pump and catheter system that is inserted using a surgical procedure. MTX110 was administered via an accelerated-dose titration/3+3 design to establish a recommended phase 2 dose (RP2D). Patients in cohort B will also receive MTX110 following a 3+3 design starting at the RP2D via a weekly infusion by the same administration method received by patients in cohort A. All patients will continue treatment until disease progression or unacceptable toxicity.

The coprimary end points are safety and identification of the RP2D. Secondary end points consist of OS, PFS, and best overall response rate.

The updated PFS and OS findings from MAGIC-G1 build upon data from another phase 1 study (NCT04264143) evaluating MTX110 in patients with newly diagnosed midline gliomas. Data presented during the 21st International Symposium on Pediatric Neuro-Oncology in July 2024 showed that patients with diffuse midline glioma (n = 9) treated with MTX110 achieved a median OS of 16.5 months (range, 12-35) and a median PFS of 10 months (range, 8-20). However, study authors noted that the trial was not powered to reliably demonstrate efficacy.^1,3

MTX110 was shown to be well tolerated in patients with diffuse midline glioma. In the phase 1 trial, 1 patient had a grade 4 adverse effect (AE), which was determined by investigators to be unrelated to treatment. Most AEs were related to infusion and were grade 2 or 3 in severity.³

The phase 1 study enrolled patients 3 to 18 years of age with diffuse midline glioma. Other eligibility criteria included a Karnofsky performance status or Lansky play-performance score of at least 70 at diagnosis, no current bleeding disorder, no medical conditions that would interfere with general anesthesia, and no severe acute infection or unexplained febrile illness.⁴

All patients received MTX110and gadolinium via convection-enhanced delivery over 9 to 11 days. Pulses 1 and 2 were prepared with MTX110 concentrations of 30 uM, 60 uM, or 90 uM.

The coprimary end points were AEs and identification of the maximum tolerated dose of MTX110. Secondary end points included PFS, OS, and steady state volume of drug distribution.

References

1. Biodexa provides update on progression free and overall survival in phase 1 study of MTX110 in recurrent glioblastoma. News release. Biodexa Pharmaceuticals PLC. October 4, 2024. Accessed October 4, 2024. https://biodexapharma.com/biodexa-provides-update-on-progression-free-and-overall-survival-in-phase-1-study-of-mtx110-in-recurrent-glioblastoma/
2. A study of intra-tumoral administered MTX110 in patients with recurrent glioblastoma (MAGIC-G1). ClinicalTrials.gov. Updated February 29, 2024. Accessed October 4, 2024. https://clinicaltrials.gov/study/NCT05324501
3. Positive phase 1 clinical data of MTX110 in DMG brain cancer demonstrating increased survival presented at ISPNO 2024. News release. Biodexa Pharmaceuticals PLC. July 2, 2024. Accessed October 4, 2024. https://biodexapharma.com/positive-phase-1-clinical-data-of-mtx110-in-dmg-brain-cancer-demonstrating-increased-survival-presented-at-ispno-2024/
4. CED of MTX110 newly diagnosed diffuse midline gliomas. ClinicalTrials.gov. Updated December 18, 2023. Accessed October 3, 2024. https://clinicaltrials.gov/study/NCT04264143