CTNI-35 - A randomized, controlled trial of Berubicin vs. Lomustine after first-line therapy for Glioblastoma Multiforme (GBM): Interim results of a pre-planned analysis of overall survival (OS)

Berubicin is an analog of doxorubicin (Dox) that appears to cross the BBB with significant central nervous system (CNS) uptake. Results of a Phase 1 dose-escalation study with 25 patients evaluable for efficacy showed 1 complete response (14+ years), 1 partial response durable for 12 weeks, and 9 patients with stable disease for a clinical benefit rate of 44%. Our current, potentially pivotal trial for patients with recurrent GBM after first-line therapy is enrolling in the US and Europe. It is unique in that all patients must be Grade 4 IDH WT, classifying these tumors as a poorer prognostic population than Grade 4 IDH mutated. Patients are randomized in a 2:1 design of Berubicin:Lomustine and stratified by MGMT methylation status. The primary endpoint is OS. Data has been presented showing that Berubicin and Lomustine arms are balanced with respect to MGMT status and demographics, with relatively comparable safety profiles (SNO Annual Meeting 2022 Abstract #383142).A pre-planned non-binding futlity analysis of the primary endpoint, OS, is being evaluated when the trial reaches ~30% of expected events (44 events). The interim analysis will be performed by an independent statistician under the supervision of the Data Safety Monitoring Board (DSMB). The futility analysis will be based on the conditional power that the trial will be positive (e.g., statistically significant difference between treatment groups’ OS). If the conditional power is < 10% then the DSMB may recommend to end the study; otherwise the study will continue as it is currently planned. The review will also include safety and secondary efficacy endpoint summaries. Results of this interim analysis will be available for the SNO annual meeting and an evaluation of its outcome will be performed, with conclusions and recommendations for the further development of Berubicin as a therapeutic option for patients with recurrent GBM.