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

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.

Timeline

Start

2026-04-01

Primary completion

2026-10-31

Completion

2032-02

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Drugs

Indications