MT-125 with radiotherapy for newly diagnosed glioblastoma

A Phase 1/2 Single-Arm Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of MT-125 Monotherapy With Radiation in Newly Diagnosed Glioblastoma

This trial tests whether adding the experimental drug MT-125 to standard radiotherapy helps people with newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Myosin Therapeutics Inc. (Industry-sponsored)
• Drugs / interventions: bevacizumab, radiation
• Locations: 3 sites (Phoenix, Arizona and 2 other locations)
• Trial ID: NCT07185880 on ClinicalTrials.gov

What this trial studies

This first-in-human Phase 1/2 trial gives escalating doses of MT-125 to adults with newly diagnosed IDH wild-type, MGMT-unmethylated glioblastoma alongside standard radiotherapy and concurrent temozolomide when indicated, with the goal of identifying the highest tolerated and recommended dose. Up to 36 participants will be enrolled across Mayo Clinic sites using a dose-escalation schema in Phase 1 and a small expansion in Phase 2. MT-125 is a CNS-penetrant small molecule inhibitor of non-muscle myosin II paralogs that reduced tumor proliferation and increased reactive oxygen species in preclinical models, producing synergy with radiation. Primary endpoints focus on safety and tolerability, with secondary assessments of preliminary efficacy and translational biomarkers.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with newly diagnosed, histologically or molecularly confirmed IDH wild-type, MGMT-unmethylated glioblastoma who have ECOG performance status 0–2 and adequate organ function.

Not a fit: Patients with recurrent disease, IDH-mutant or MGMT-methylated tumors, significant organ dysfunction, or those unable to receive concurrent radiotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, MT-125 could make radiotherapy more effective against GBM and slow tumor growth in patients with IDH wild-type, MGMT-unmethylated tumors.

How similar studies have performed: This is the first-in-human trial of MT-125; preclinical data showed radiosensitization but NMII-targeting treatments have not yet been proven effective in human GBM.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent form (ICF).
2. New Diagnosed with histologically or molecularly confirmed IDH wild type and MGMT unmethylated GBM.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
4. The following laboratory values obtained ≤15 days prior to registration:

   1. Hemoglobin ≥9.0 g/dL
   2. Absolute neutrophil count (ANC) ≥1500/mm3
   3. Platelet count ≥100,000/mm3
   4. Total bilirubin ≤1.5 x upper limit of normal (ULN)
   5. Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN (or ≤5 x ULN for participants with liver involvement)
   6. Prothrombin time (PT)/ International normalized ratio (INR)/ Activated partial thromboplastin time (aPTT) ≤1.5 x ULN OR if participant is receiving anticoagulant therapy and INR or aPTT is within target range of therapy
   7. Serum eGFR ≥60 ml/min
5. QTc 470 ms on triplicate 12 lead ECG ≤29 days prior to registration. NOTE: QTc intervals will be corrected using Fridericia's formula (Fridericia 1920)
6. Echocardiographic Assessment: Left Ventricular Ejection Fraction (LVEF) ≥ 55%.
7. Negative serum pregnancy test done ≤7 days prior to first dose of MT-125 administration, for persons of childbearing potential only.

   a. If \>7 days between last test and first dose of study treatment, the serum pregnancy test will be repeated.
8. Has provided written informed consent.
9. Ability to complete questionnaire(s) by themselves or with assistance.
10. Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
11. On a stable dose of steroids for at least 2 weeks prior to enrollment

Exclusion Criteria:

1. Any of the following because this study involves an investigational agent, the genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and newborn are unknown:

   1. Pregnant persons
   2. Nursing persons
   3. Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception.
2. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
3. Receiving any other investigational agent.
4. Any concomitant disease, condition, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the Investigator or Sponsor, pose an unacceptable risk to the participant in the study or interfere with the interpretation of study data.

Where this trial is running

Phoenix, Arizona and 2 other locations

• Mayo Clinic Hospital — Phoenix, Arizona, United States (Recruiting)
• Mayo Clinic Hospital — Jacksonville, Florida, United States (Recruiting)
• Mayo Clinic Hospital — Rochester, Minnesota, United States (Recruiting)

Conditions Glioblastoma; MGMT unmethylated GBM; IDH wild type; small molecule; MT-125; newly diagnosed; O6-methylguanine- DNA methyltransferase; GBM