Phase 1/2 MT-125 non-muscle myosin II (IIA/IIB) inhibitor with chemoradiation in GBM

Myosin Therapeutics’ Phase 1/2 NOVA-GBM study tests MT-125, a CNS-penetrant small-molecule inhibitor of non-muscle myosin II paralogs IIA and IIB, given alongside standard chemoradiation for newly diagnosed glioblastoma. Phase 1 is single-arm dose escalation (up to four dose levels; 5 days on/2 days off during the 6-week radiotherapy + temozolomide course) using a Bayesian Optimal Interval design to define dose-limiting toxicities, MTD, pharmacokinetics, and the recommended Phase 2 dose. Phase 2 is a randomized parallel expansion at the MTD and one dose below to refine tolerability and look for early efficacy signals in a more controlled way. Eligible patients have IDH-wildtype, MGMT promoter–methylated GBM (MGMT methylation is a common subtype and is associated with better temozolomide responsiveness), making this a rational setting to test whether cytoskeletal “mechanobiology” targeting can deepen benefit on top of the current backbone of maximal safe resection followed by radiotherapy with concurrent and adjuvant temozolomide.