Surgical Window Study of CM93 in Subjects With Recurrent Glioblastoma (rGBM) - NCT07927491

Sponsor: NYU Langone Health Conditions: Recurrent Glioblastoma With EGFR Mutation This is an open-label, first-in-human phase 1 and surgical window of opportunity study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of CM93 in subjects with recurrent glioblastoma (rGBM) characterized by Epidermal Growth Factor Receptor (EGFR) amplification/mutation who have previously received at least 1st-line high-grade glioma therapy. The study will be conducted in 2 consecutive parts - Part 1: Dose Escalation and Dose Expansion Part 2: Window-of-Opportunity Surgical Study Part 1 of the study will consist of a Dose Escalation and a Dose Expansion Phase. The Dose Escalation Phase will employ a Bayesian Optimal Interval (BOIN) dose escalation design to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and ecommended Phase 2 dose(s) (RP2D). The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of the study subjects. Part 2 of the study is a surgical window of opportunity study in which patients with EGFR-altered recurrent glioblastoma will be randomized 1:1 to pre-treatment with CM93 (CM93-pre-treated cohort) versus no pretreatment (control cohort) prior to surgical resection to determine whether CM93 crosses the blood-brain barrier and achieves therapeutic concentrations in the tumor (CM93-pre-treated cohort only), and whether it effectively inhibits EGFR activation in tumor tissue (comparison of CM93-pre-treated cohort versus control cohort).