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).
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..
Hemoglobin ≥9.0 g/dL
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.
Parallel
MT-125
DrugThis is an investigational new drug under IND 170975.
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.
Incidence and Severity of AEs
Incidence and Severity, attribution, grade and type of AE will be assessed based on the NCI CTCAE v5.
Maximum Tolerated Dose
To determine the maximum tolerated dose (MTD) of MT-125
PK Parameters- Cmax
The time it takes for a drug to reach a maximum concentration after administration.
PK Parameters-AUC 0-24hr
Area under the plasma concentration-time curve over the last 24 hour dosing interval.
PK Parameters - T1/2
Time required for plasma concentrations of a drug to decrease by 50%
To obtain preliminary data on clinical efficacy measurements such as ORR
Overall Response Rate in those with Measurable disease
Exploratory Analysis to obtain preliminary data on clinical efficacy
6 month Progression Free survival (PFS6) based on MRI imaging
To obtain preliminary data on clinical efficacy
Overall Survival (OS)
Click on the lead sponsor to view all of their trials.
Myosin Therapeutics Inc.
Lead sponsor
Mayo Clinic
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
