A Phase 1/2 Study of the Safety and Tolerability of MT-125 in GBM Patients

NCT07185880 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: MT-125-GBM-101R44CA278293
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of the study is to determine the recommended dose and further understand the safety of MT-125 in participants who have been diagnosed with glioblastoma, a primary brain tumor, when administered in combination with your standard of care treatment. Initially, participants with newly diagnosed glioblastoma will be given different doses of MT-125 in combination with radiotherapy (RT) with the goal of identifying the highest tolerated dose. Up to 36 people with glioblastoma who are at least18 years old are being invited to join this study. MT-125 is a type of study treatment which acts on cancer cells in the brain to destroy them. It will be administered on the same day as your standard of care radiotherapy because it is also designed to help radiotherapy work better. However, this is the first time MT-125 will be studied in humans. Therefore, the use is considered investigational. If you would like more details about MT-125 in glioblastoma participants, please ask the Study Doctor. You will be among the first participants with glioblastoma to receive this study treatment. Its safety and effectiveness have not yet been established in humans. Thus, we do not know whether it will work for you. Your condition may improve, may get worse, or there may be no change. The selected participant population-individuals newly diagnosed with histologically and/or molecularly confirmed IDH wild-type, MGMT-unmethylated glioblastoma-represents those least likely to experience safety concerns or adverse events related to the study treatment, and most likely to derive therapeutic benefit. There are certain tests/questions you must complete to find out if you meet the requirements to be in the study. If you do not meet these requirements, you cannot take part in the study. If this happens, you can talk to your Study Doctor about other options.

Conditions

Glioblastoma (GBM)

Keywords

Glioblastoma; MGMT unmethylated GBM; IDH wild type; small molecule; MT-125; newly diagnosed; O6-methylguanine- DNA methyltransferase; GBM; isocitrate dehydrogenase (IDH) wild type; non-muscle myosin II

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity Measurement

  The dose escalation portion of this study will follow a BOIN design with cohorts containing a min of 3 DLT evaluable participants. If the observed DLT rate at the current dose is ≤0.236, then the decision will be to escalate the dose to the next higher dose level; if the observed DLT rate at the current dose is \>0.359, then the decision will be to deescalate the dose to the next lower dose level; otherwise, the decision will be to stay at the current dose level.

  From Day 1 through 6 weeks of treatment

• Incidence and Severity of AEs

  Incidence and Severity, attribution, grade and type of AE will be assessed based on the NCI CTCAE v5.

  From Day 1 through 6 weeks of treatment

Secondary Outcomes (8)

• Maximum Tolerated Dose

  Day 1 through Day 40

• PK Parameters- Cmax

  Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40

• PK Parameters - Tmax

  Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40

• PK Parameters-AUC 0-24hr

  Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40

• PK Parameters - T1/2

  Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40

Other Outcomes (3)

• To obtain preliminary data on clinical efficacy measurements such as ORR

  Day 1 though on average one year following completion of treatment

• Exploratory Analysis to obtain preliminary data on clinical efficacy

  Up to 1 year following completion of treatment

• To obtain preliminary data on clinical efficacy

  Day 1 though on average one year following completion of treatment.

Study Arms (5)

MT-125 at 25 mg

EXPERIMENTAL

Up to 6 participants will receive 25 mg of MT-125 for 5 days, then off 2 days for a total of 6 weeks in combination with radiation therapy.

Drug: MT-125

MT-125 at 50 mg

EXPERIMENTAL

Up to 6 participants will receive 50 mg of MT-125 for 5 days, then off 2 days for a total of 6 weeks in combination with radiation therapy.

Drug: MT-125

MT-125 at 83.5mg

EXPERIMENTAL

Up to 6 participants will receive 83.5 mg of MT-125 for 5 days, then off 2 days for a total of 6 weeks in combination with radiation therapy.

Drug: MT-125

MT-125 at 100 mg

EXPERIMENTAL

Up to 6 participants will receive 100 mg of MT-125 for 5 days, then off 2 days for a total of 6 weeks in combination with radiation therapy.

Drug: MT-125

MT-125 at MTD and one dose lower than MTD

EXPERIMENTAL

Participants will be randomized to receive either MTD or one dose lower than MTD for 5 days, then off 2 days for a total of 6 weeks in combination with radiation therapy.

Drug: MT-125

Interventions

MT-125 DRUG

This is an investigational new drug under IND 170975.

MT-125 at 100 mg; MT-125 at 25 mg; MT-125 at 50 mg; MT-125 at 83.5mg; MT-125 at MTD and one dose lower than MTD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of signing the informed consent form (ICF).
• New Diagnosed with histologically or molecularly confirmed IDH wild type and MGMT unmethylated GBM.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2.
• The following laboratory values obtained ≤15 days prior to registration:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1500/mm3
• Platelet count ≥100,000/mm3
• Total bilirubin ≤1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN (or ≤5 x ULN for participants with liver involvement)
• 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
• Serum eGFR ≥60 ml/min
• 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)
• Echocardiographic Assessment: Left Ventricular Ejection Fraction (LVEF) ≥ 55%.
• 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.

You may not qualify if:

• 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:
• Pregnant persons
• Nursing persons
• Persons of childbearing potential and persons able to father a child who are unwilling to employ adequate contraception.
• 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.
• Receiving any other investigational agent.
• 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.

Sponsors & Collaborators

• Myosin Therapeutics Inc.: lead
• Mayo Clinic: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

RECRUITING

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

RECRUITING

Mayo Clinic Hospital

Rochester, Minnesota, 55905, United States

RECRUITING

Related Publications (8)

• Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010 Apr 10;28(11):1963-72. doi: 10.1200/JCO.2009.26.3541. Epub 2010 Mar 15.

  PMID: 20231676 BACKGROUND

• Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.

  PMID: 15758009 BACKGROUND

• Hegi ME, Genbrugge E, Gorlia T, Stupp R, Gilbert MR, Chinot OL, Nabors LB, Jones G, Van Criekinge W, Straub J, Weller M. MGMT Promoter Methylation Cutoff with Safety Margin for Selecting Glioblastoma Patients into Trials Omitting Temozolomide: A Pooled Analysis of Four Clinical Trials. Clin Cancer Res. 2019 Mar 15;25(6):1809-1816. doi: 10.1158/1078-0432.CCR-18-3181. Epub 2018 Dec 4.

  PMID: 30514777 BACKGROUND

• Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. doi: 10.1056/NEJMoa043331.

  PMID: 15758010 BACKGROUND

• Melhem JM, Detsky J, Lim-Fat MJ, Perry JR. Updates in IDH-Wildtype Glioblastoma. Neurotherapeutics. 2022 Oct;19(6):1705-1723. doi: 10.1007/s13311-022-01251-6. Epub 2022 May 31.

  PMID: 35641844 BACKGROUND

• Kenchappa RS, Radnai L, Young EJ, Zarco N, Lin L, Dovas A, Meyer CT, Haddock A, Hall A, Toth K, Canoll P, Nagaiah NKH, Rumbaugh G, Cameron MD, Kamenecka TM, Griffin PR, Miller CA, Rosenfeld SS. MT-125 inhibits non-muscle myosin IIA and IIB and prolongs survival in glioblastoma. Cell. 2025 Aug 21;188(17):4622-4639.e19. doi: 10.1016/j.cell.2025.05.019. Epub 2025 Jun 10.

  PMID: 40499543 BACKGROUND

• Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.

  PMID: 27407096 BACKGROUND

• Liu S, Yuan Y. Bayesian optimal interval designs for phase I clinical trials. Journal of the Royal Statistical Society: Series C (Applied Statistics). 2015;64(3):507-23.

  BACKGROUND

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a FIH, phase 1/2, open-label, single arm dose escalation study of MT-125. There will be up to 4 dose levels in the dose escalation phase, followed by a dose expansion phase. The dose expansion cohorts will follow a randomized, parallel design with two dose levels determined as the MTD and the dose below the MTD. This study will determine the safety and tolerability of MT-125 administered 5 consecutive days followed by 2 days off per week for the 6 weeks of outpatient RT in participants with newly diagnosed IDH wild-type and MGMT unmethylated GBM. Each dose escalation cohort will enroll no more than 6 total participants.

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: September 22, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): February 1, 2032
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)