Abstract
Berubicin is a doxorubicin (Dox) analog that appears to cross the BBB with significant central nervous system (CNS) uptake. Berubicin prolongs survival in orthotopic mouse intracranial models with greater infiltration of the tumor compared to normal tissue. A Phase 1 dose-escalation study showed myelosuppression as the dose-limiting toxicity, with 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%. A trial of Berubicin vs Lomustine in patients with recurrent GBM after first-line therapy in the US and Europe is enrolling patients in a 2:1 randomization design of Berubicin:Lomustine. Patients will be stratified by MGMT methylation status. The primary endpoint is overall survival (OS). A pre-planned, non-binding futility analysis will be performed after approximately 30 to 50% of all planned patients have reached the primary endpoint. Currently, 97 patients are enrolled with 65 in the Berubicin arm and 32 in the Lomustine arm. At present these patients show comparable demographics, with an unmethylated MGMT population of ~60% in both arms. Patients with all grades of adverse events were 80% and 69% on the Berubicin and Lomustine arms, respectively. Grade 3-4 events were 43% (Berubicin arm) and 38% (Lomustine arm), although less than or equal to 5% of patients discontinued the study due to these events. The data available shows that Berubicin and Lomustine arms are presently balanced with relatively comparable safety profiles. The study is continuing to evaluate the efficacy of this novel drug candidate and potentially provide therapeutic options for patients after first-line therapy. An updated profile of the patient population, safety, and initial efficacy will be presented.