MTX110 May Show Survival Benefits in Recurrent Glioblastoma

Developers designed MTX110 as a water-soluble form of panobinostat free base via complexation with hydroxypropyl-β-cyclodextrin, which may facilitate convection-enhanced delivery at potentially chemotherapeutic doses directly to a brain tumor.

Treatment with MTX110, an investigational formulation of panobinostat (Farydak) in combination with a convection-enhanced delivery pump/catheter system, showed a potential overall survival (OS) and progression-free survival (PFS) benefit among a small group of patients with recurrent glioblastoma, according to findings from the phase 1 MAGIC-1 study (NCT05324501).¹

As previously reported, the OS among patient 1 and patient 2 in cohort A was 12 months and 13 months, respectively. Follow-up is ongoing for the 2 remaining patients in this cohort. Data showed an OS of 13 months and a PFS of 6 months for patient 3. Additionally, the OS and PFS were both 12 months for patient 4 to date, who showed no signs of disease progression.

According to the press release, findings from the MAGIC-1 study build upon prior reports of MTX110 showing promise in those with diffuse midline glioma in another phase 1 study (NCT04264143). Investigators presented data from the diffuse midline glioma trial at the 21st International Symposium on Paediatric Neuro-Oncology (ISPNO 2024).² Findings showed that the median OS was 16.5 months in 9 patients following 2 infusions of MTX110; 1 patient received the agent at the optimum dose.

Developers designed MTX110 as a water-soluble form of panobinostat free base via complexation with hydroxypropyl-β-cyclodextrin, which may facilitate convection-enhanced delivery at potentially chemotherapeutic doses directly to a brain tumor. According to the developers, the standard, orally available form of panobinostat is not recommended for use in patients with brain cancer due to its poor ability to penetrate the blood-brain barrier and inadequate brain drug concentrations.

MTX110 may overcome this obstacle through administration with a catheter system to break through the blood-brain barrier. This method of dosing may expose brain tumors to higher drug concentrations while reducing systemic drug levels and potentially limiting toxicity or adverse effects.

Investigators designed the phase 1 MAGIC-1 study to assess the feasibility, safety, and efficacy of administering MTX110 to patients with recurrent glioblastoma. In cohort A, patients will receive weekly doses of MTX110 via convection-enhanced delivery until unacceptable toxicity or disease progression.³ In cohort B, patients will receive the same dose of MTX110 and have the option to reposition the catheter at the time of disease progression; weekly dosing of MTX110 will then continue until the next incidence of unacceptable toxicity or progressive disease.

The trial’s primary end points are the safety of MTX110 and the recommended phase 2 dose. Secondary end points include OS, PFS, and best overall response rate.

Patients 18 years and older with recurrent glioblastoma who are healthy enough to tolerate surgery and general anesthesia are eligible for enrollment. Having an estimated life expectancy of more than 3 months is another requirement for enrollment.

Those who are scheduled to undergo re-irradiation for a recurrent tumor or have a history of treatment for glioblastoma that includes the use of carmustine (Gliadel) wafers are ineligible for MAGIC-1 enrollment. Patients are also unable to enroll if they have no eligibility to undergo MRI; treatment with tumor treating fields within 1 week prior to beginning treatment with MTX101; neoplastic lesions in the brainstem, cerebellum, or spinal cord; or posterior fossa location of the tumor, regardless of the morphology.

Additionally, patients cannot have a prior unrelated malignancy requiring current active treatment apart from cervical carcinoma in situ and adequately managed basal cell or squamous cell carcinoma of the skin.

References

1. Biodexa's MX-110 continues to show promise in recurrent glioblastoma (rGBM), the deadliest brain cancer. News release. Biodexa Pharmaceuticals PLC. October 17, 2024. Accessed October 18, 2024. https://tinyurl.com/24z5jxud
2. 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 18, 2024. https://tinyurl.com/2p9aku6v
3. A study of intra-tumoral administered MTX110 in patients with recurrent glioblastoma (MAGIC-G1). ClinicalTrials.gov. Updated February 29, 2024. Accessed October 18, 2024. https://tinyurl.com/4jxka4bv