GlioblastomaPhase 1/2NOVA-GBMNCT07604285
A Phase 1/2 Study of Safety and Tolerability of MT-125 With Chemoradiation in Patients With Newly Diagnosed MGMT Methylated Glioblastoma
A Phase 1/2 study testing MT-125 in people with Glioblastoma, run by Myosin Therapeutics Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- MT-125
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2026to Mar 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 19Show fewer
- 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.
- If >7 days between last test and first dose of study treatment, the serum pregnancy test will be repeated.
- Has provided written informed consent.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
- On a stable dose of steroids for at least 2 weeks prior to enrollment
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
Mayo Clinic Hospital
Jacksonville, Florida, 32224
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Wendy J Sherman, MD
Mayo Clinic Hospital
Phoenix, Arizona, 85054
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Shannon F Fortin-Ensign, MD, PhD
Mayo Clinic Hospital
Rochester, Minnesota, 55905
Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu
Ugur Sener, MD
About this study
Official title: A Phase 1/2 Dose Escalation and Randomized Expansion Study of Safety, Tolerability, and Pharmacokinetics of MT-125 Monotherapy With Chemoradiation in Patients With Newly Diagnosed MGMT Methylated Glioblastoma
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).
Read the detailed description
MT-125 is a potent, selective, and central nervous system (CNS) permeable dual small molecule inhibitor of the non-muscle myosin II (NMII) paralogs, IIA and IIB. MT-125 is being developed by Myosin Therapeutics Inc. as a potential treatment for glioblastoma (GBM). NMIIs are molecular motor ATPases that act directly on actin to regulate the cytoskeleton's control of cellular processes such as movement, division, signaling and mitochondrial biology. As a result, simultaneous inhibition of NMIIA and IIB with MT-125 interferes with tumor cell proliferation, invasion and metastasis, while also generating reactive oxygen species (ROS) in tumor cells. The latter is due to the role of NMII in mitochondrial quality control and underlies the synergistic survival benefit observed in preclinical studies when MT-125 and radiation therapy (RT) are combined. Additionally, NMIIA is upregulated in several types of cancer, including GBM, speaking to its importance in cancer physiology and making these tumor cells highly sensitive to its inhibition. The focus of this clinical study is GBM.
Patients with GBM have a poor prognosis, and there have been no new Food and Drug Administration (FDA) approved drugs for these patients since 2008, when bevacizumab was approved. The current well-known standard of care for newly diagnosed GBM is maximal safe surgical resection followed by concurrent RT with temozolomide (TMZ). O6-methylguanine- DNA methyltransferase (MGMT) promoter methylation status is the most predictive biomarker for TMZ responsiveness, where patients with unmethylated MGMT do not respond to TMZ.
MT-125 significantly prolongs survival as a monotherapy in animal models and is synergistic with both RT and with FDA-approved oncogenic kinase inhibitors to further enhance survival. The Sponsor is currently evaluating MT-125 as a monotherapy in a first-in-human (FIH) trial (STAR-GBM) with standard of care RT in newly diagnosed isocitrate dehydrogenase (IDH) wildtype / MGMT unmethylated GBM. Due to the poor response of MGMT unmethylated tumors to TMZ, the chemotherapeutic is excluded in the STAR-GBM trial. Here we will evaluate MT-125 as a monotherapy in a Phase 1/2 trial (NOVA-GBM) in newly diagnosed IDH wildtype / MGMT methylated GBM with standard of care RT and TMZ, following the standard chemoradiation treatment regimen.
In the pivotal 28-day nonclinical safety studies of MT-125, no dose-limiting toxicities (DLT) or adverse effects (AE) were noted in any of the parameters evaluated (clinical observations, functional endpoints, clinical pathology, macroscopic and histologic tissue assessments) at doses up to the NOAELs, 20 mg/kg/day and 30 mg/kg/day in dogs and rats, respectively, which yielded systemic MT-125 exposures 10- to 16-fold greater than efficacious exposures in pharmacodynamic in vivo models. As the NOAELs in both studies were below the STD10 (rats) and HNSTD (dogs), the calculated safety margins are conservative.
The goal of this Phase 1/2, MT-125 dose escalation and expansion study is to evaluate the safety and tolerability of MT-125 administered 5 consecutive days per week with 2 days off for the 6 weeks of outpatient RT plus TMZ. Participants with newly diagnosed GBM with histologically or molecularly confirmed IDH wildtype and MGMT methylation will be eligible to enroll. The DLT observation window will be 6 weeks following first treatment administration, and a Bayesian Optimal Interval (BOIN) trial design will be used to efficiently evaluate up to four dose levels. Secondary endpoints for this Phase 1/2 study will include determining the maximum tolerated dose (MTD), which will contribute to the selection of the recommended phase 2 dose (RP2D) and evaluating the systemic pharmacokinetics (PK) of MT-125.
Once the MTD is determined, additional participants will be enrolled into a randomized, parallel dose expansion cohort, consisting of up to 2 potential doses of MT-125. The dose levels for the expansion cohort will be selected as the MTD and the dose below the MTD. Overall response rate (ORR) in those participants with measurable disease, progression-free survival (PFS6) in all participants, and Overall Survival (OS) in all participants are included as exploratory endpoints
If no MTD is identified within the initially defined dose range and all tested doses are deemed well-tolerated based on the observed DLTs, the study may be paused temporarily to allow consideration of dose levels beyond those originally planned.
- Conditions
- Glioblastoma
- Being tested
- MT-125
- 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
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MT-125Drug
This is an investigational new drug under IND 170975.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: MT-125 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 1 through 6 weeks of treatment
Secondary outcomes (7)
Maximum Tolerated Dose
To determine the maximum tolerated dose (MTD) of MT-125
Measured: Day 1 through Day 40
PK Parameters- Cmax
The time it takes for a drug to reach a maximum concentration after administration.
Measured: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters-AUC 0-24hr
Area under the plasma concentration-time curve over the last 24 hour dosing interval.
Measured: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters - T1/2
Time required for plasma concentrations of a drug to decrease by 50%
Measured: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters - CL
CL will quantify the body's efficiency in eliminating MT-125
Measured: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters - Vss
The steady state volume of distribution that describes how MT-125 distributes throughout the body once it has reached a state of equilibrium.
Measured: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
Determine the phase 2 dose
To determine the Recommended Phase 2 Dose (RP2D) of MT-125
Measured: Day 1 through 6 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2026
- Study startJul 2026 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Myosin Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07604285
- Sponsor's protocol ID
- MT-125-GBM-201
- Other IDs
- 26C19
- Acronym
- NOVA-GBM
- Status last verified
- May 2026
- First submitted
- 18 May 2026
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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. . : . .
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.
PubMed 27407096Kenchappa 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.
PubMed 40499543Melhem 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.
PubMed 35641844Hegi 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.
PubMed 15758010Hegi 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.
PubMed 30514777Stupp 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.
PubMed 15758009Wen 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.
PubMed 20231676
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Dose Escalation and Randomized Expansion Study of Safety, Tolerability, and Pharmacokinetics of MT-125 Monotherapy With Chemoradiation in Patients With Newly Diagnosed MGMT Methylated Glioblastoma
- ClinicalTrials.gov ID
- NCT07604285
- Acronym / sponsor ID
- NOVA-GBM / MT-125-GBM-201
- Conditions
- Glioblastoma
- Keywords
- Glioblastoma, MGMT methylated GBM, IDH wild type, small molecule, MT-125, newly diagnosed, O6-methylguanine- DNA methyltransferase, GBM
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Myosin Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic
- Study start
- Jul 2026 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 22 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
MT-125 is a potent, selective, and central nervous system (CNS) permeable dual small molecule inhibitor of the non-muscle myosin II (NMII) paralogs, IIA and IIB. MT-125 is being developed by Myosin Therapeutics Inc. as a potential treatment for glioblastoma (GBM). NMIIs are molecular motor ATPases that act directly on actin to regulate the cytoskeleton's control of cellular processes such as movement, division, signaling and mitochondrial biology. As a result, simultaneous inhibition of NMIIA and IIB with MT-125 interferes with tumor cell proliferation, invasion and metastasis, while also generating reactive oxygen species (ROS) in tumor cells. The latter is due to the role of NMII in mitochondrial quality control and underlies the synergistic survival benefit observed in preclinical studies when MT-125 and radiation therapy (RT) are combined. Additionally, NMIIA is upregulated in several types of cancer, including GBM, speaking to its importance in cancer physiology and making these tumor cells highly sensitive to its inhibition. The focus of this clinical study is GBM.
Patients with GBM have a poor prognosis, and there have been no new Food and Drug Administration (FDA) approved drugs for these patients since 2008, when bevacizumab was approved. The current well-known standard of care for newly diagnosed GBM is maximal safe surgical resection followed by concurrent RT with temozolomide (TMZ). O6-methylguanine- DNA methyltransferase (MGMT) promoter methylation status is the most predictive biomarker for TMZ responsiveness, where patients with unmethylated MGMT do not respond to TMZ.
MT-125 significantly prolongs survival as a monotherapy in animal models and is synergistic with both RT and with FDA-approved oncogenic kinase inhibitors to further enhance survival. The Sponsor is currently evaluating MT-125 as a monotherapy in a first-in-human (FIH) trial (STAR-GBM) with standard of care RT in newly diagnosed isocitrate dehydrogenase (IDH) wildtype / MGMT unmethylated GBM. Due to the poor response of MGMT unmethylated tumors to TMZ, the chemotherapeutic is excluded in the STAR-GBM trial. Here we will evaluate MT-125 as a monotherapy in a Phase 1/2 trial (NOVA-GBM) in newly diagnosed IDH wildtype / MGMT methylated GBM with standard of care RT and TMZ, following the standard chemoradiation treatment regimen.
In the pivotal 28-day nonclinical safety studies of MT-125, no dose-limiting toxicities (DLT) or adverse effects (AE) were noted in any of the parameters evaluated (clinical observations, functional endpoints, clinical pathology, macroscopic and histologic tissue assessments) at doses up to the NOAELs, 20 mg/kg/day and 30 mg/kg/day in dogs and rats, respectively, which yielded systemic MT-125 exposures 10- to 16-fold greater than efficacious exposures in pharmacodynamic in vivo models. As the NOAELs in both studies were below the STD10 (rats) and HNSTD (dogs), the calculated safety margins are conservative.
The goal of this Phase 1/2, MT-125 dose escalation and expansion study is to evaluate the safety and tolerability of MT-125 administered 5 consecutive days per week with 2 days off for the 6 weeks of outpatient RT plus TMZ. Participants with newly diagnosed GBM with histologically or molecularly confirmed IDH wildtype and MGMT methylation will be eligible to enroll. The DLT observation window will be 6 weeks following first treatment administration, and a Bayesian Optimal Interval (BOIN) trial design will be used to efficiently evaluate up to four dose levels. Secondary endpoints for this Phase 1/2 study will include determining the maximum tolerated dose (MTD), which will contribute to the selection of the recommended phase 2 dose (RP2D) and evaluating the systemic pharmacokinetics (PK) of MT-125.
Once the MTD is determined, additional participants will be enrolled into a randomized, parallel dose expansion cohort, consisting of up to 2 potential doses of MT-125. The dose levels for the expansion cohort will be selected as the MTD and the dose below the MTD. Overall response rate (ORR) in those participants with measurable disease, progression-free survival (PFS6) in all participants, and Overall Survival (OS) in all participants are included as exploratory endpoints
If no MTD is identified within the initially defined dose range and all tested doses are deemed well-tolerated based on the observed DLTs, the study may be paused temporarily to allow consideration of dose levels beyond those originally planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| MT-125 at 25 mg | Experimental | Drug: MT-125Up 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 |
| MT-125 at 50 mg | Experimental | Drug: MT-125Up 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 |
| MT-125 at 83.5 mg | Experimental | Drug: MT-125Up 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 |
| MT-125 at 100 mg | Experimental | Drug: MT-125Up 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 |
| MT-125 at MTD and one dose lower than MTD | Experimental | Drug: MT-125Participants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- 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)
Key exclusion criteria (8 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MT-125This is an investigational new drug under IND 170975. | Drug | 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 |
Primary outcome
Dose Limiting Toxicity Measurement
Time frame: Day 1 through 6 weeks of treatment
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.
Incidence and Severity of AEs
Time frame: Day 1 through 6 weeks of treatment
Incidence and Severity, attribution, grade and type of AE will be assessed based on the NCI CTCAE v5.
7 secondary outcomes
Maximum Tolerated Dose
Time frame: Day 1 through Day 40
PK Parameters- Cmax
Time frame: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters-AUC 0-24hr
Time frame: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters - T1/2
Time frame: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters - CL
Time frame: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
PK Parameters - Vss
Time frame: Completed on study days; Day 1, Day 2, Day 5, Day 19, Day 33 and Day 40
Determine the phase 2 dose
Time frame: Day 1 through 6 weeks of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- BackgroundLiu 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: PubMed 27407096Yuan 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.
- Background: PubMed 40499543Kenchappa 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.
- Background: PubMed 35641844Melhem 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.
- Background: PubMed 15758010Hegi 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.
- Background: PubMed 30514777Hegi 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.
- Background: PubMed 15758009Stupp 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.
- Background: PubMed 20231676Wen 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MT-125 in people with Glioblastoma, run by Myosin Therapeutics Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity Measurement (time frame: Day 1 through 6 weeks of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07604285, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.