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

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.

Sex

All

Minimum age

18 Years

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.

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