OLIG2 Inhibitor CT-179 for Recurrent and Newly-diagnosed Glioblastoma

The OPAL trial is a Phase 1, multi-center, open-label study designed to evaluate the safety and tolerability of CT-179. CT-179 is an orally administered small molecule that modulates the oligodendrocyte transcription factor 2 (OLIG2). The study will enroll up to 54 adult patients with isocitrate dehydrogenase (IDH)-wild type Glioblastoma (GBM).

To evaluate the drug across different stages of the disease, the trial is structured into distinct treatment groups:

* Treatment Arm 1 (Recurrent GBM): In Treatment Arm 1, patients will receive a daily oral dose of CT-179 for a 28-day Dose-Limiting Toxicity (DLT) assessment period. Dose escalation begins at 0.65 mg/kg and may proceed up to 10.4 mg/kg across six planned cohorts. The first three cohorts will use an Accelerated Titration design (one patient per cohort) before reverting to a standard 3+3 dose-escalation design if specific moderate or dose-limiting toxicities are observed. * Treatment Arm 2 (Newly Diagnosed MGMT-Unmethylated GBM):

Enrollment in Arm 2 will only begin after the sixth cohort in Arm 1 successfully clears its 28-day DLT period. These patients will receive CT-179 for a one-week lead-in, followed by six weeks of CT-179 administered concurrently with standard radiation therapy (60 Gy). The DLT observation period for this arm lasts up to 12 weeks and uses a standard 3+3 dose-escalation design.

* Intra-Tumoral Drug Concentration (IDC) Sub-Study: Once the Maximum Tolerated Dose (MTD) is established in Arm 1, a sub-study will evaluate how well CT-179 penetrates tumor tissue. Patients will receive CT-179 for 7 to 14 days before their scheduled tumor resection so that intra-tumoral drug concentrations can be measured from the resected tissue. * Study Objectives: The primary objective across all cohorts is to determine the MTD and the Recommended Phase 2 Dose (RP2D) for CT-179. Secondary and exploratory measures include tracking pharmacokinetics (PK), assessing preliminary efficacy via Overall Response Rate (ORR) and Progression-Free Survival (PFS) using RANO 2.0 criteria, and evaluating changes in tumor metabolism via FET-PET imaging.

• Incidence of Adverse Events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 [Срок оценки: From first dose of CT-179 through 28 days after the last dose of study treatment, assessed for up to 24 months.]
• Pharmacokinetic parameters Tmax [Срок оценки: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
• Overall response rate (ORR) [Срок оценки: From first dose of CT-179 until documented disease progression or withdrawal, assessed for up to 24 months.]
• Progression-Free Survival (PFS) [Срок оценки: From first dose of CT-179 to first documented disease progression, assessed for up to 24 months.]
• Pharmacokinetic parameters Cmax [Срок оценки: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
• Pharmacokinetic parameters T1/2 [Срок оценки: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]
• Pharmacokinetic parameters AUC [Срок оценки: From first dose of CT-179 through the end of treatment, assessed for up to 24 months.]