A Phase 1/2 Study of Safety and Tolerability of MT-125 With Chemoradiation in Patients With Newly Diagnosed MGMT Methylated Glioblastoma

NCT07604285 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: MT-125-GBM-20126C19
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, single-arm MT-125 dose escalation study followed by a Phase 2, randomized parallel design dose expansion phase, to determine the safety and tolerability of MT-125 administered 5 consecutive days a week with 2 days off for the 6 weeks of outpatient treatment of Radiotherapy (RT) plus TMZ. Participants with newly diagnosed histologically or molecularly confirmed IDH wild type and MGMT methylated GBM will be eligible to enroll. The dose-limiting toxicity (DLT) observation window will be 6 weeks, starting with the first dose of MT-125 administration and chemoradiation. A Bayesian Optimal Interval (BOIN) adaptive trial design will be used to efficiently evaluate up to four dose levels. Secondary endpoints for this Phase 1/2 study will include determination of the MTD, the systemic PK of MT-125, and the RP2D of MT-125. Once the MTD is defined, additional participants will be enrolled as part of an expansion cohort, with a randomized parallel design, which will include up to 2 dose levels which are expected to be MTD and one dose below the MTD. Up to 36 participants will be enrolled in the study (up to 24 participants in the dose escalation phase and up to a total of 12 participants maximum per dose level for the two expansion cohorts).

Conditions

Glioblastoma

Keywords

Glioblastoma; MGMT methylated 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.

  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.

  Day 1 through 6 weeks of treatment

Secondary Outcomes (7)

• 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-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

• PK Parameters - CL

  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 for 2 days for a total of 6 weeks in combination of RT plus TMZ

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 for 2 days for a total of 6 weeks in combination of RT plus TMZ

Drug: MT-125

MT-125 at 83.5 mg

EXPERIMENTAL

Up to 6 participants will receive 83.5 mg of MT-125 for 5 days then off for 2 days for a total of 6 weeks in combination of RT plus TMZ

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 for 2 days for a total of 6 weeks in combination of RT plus TMZ

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 RT plus TMZ

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 83.5 mg; 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 wildtype and MGMT methylated 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 (see Appendix 2 for highly effective forms of 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.
• Other active malignancy requiring therapy such as RT, chemotherapy, or immunotherapy. Participants on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria. NOTE: Participants with malignancies under active surveillance are still eligible.

Sponsors & Collaborators

• Myosin Therapeutics Inc.: lead
• Mayo Clinic: collaborator

Study Sites (3)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic Hospital

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Hospital

Rochester, Minnesota, 55905, United States

Location

Related Publications (8)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a FIH, Phase 1, single-arm MT-125 dose escalation study followed by a Phase 2, randomized parallel design dose expansion phase. 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 plus TMZ in participants with newly diagnosed IDH wildtype and MGMT methylated GBM. Each dose escalation cohort will enroll at least 3 participants and no more than 6 total. The DLT observation window will be from the first dose through 6 weeks of MT-125 and RT plus TMZ, and a BOIN adaptive trial design will be used to efficiently evaluate up to four dose levels.

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 22, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)