PB1743 LIPOSOMAL ANNAMYCIN ‐ A NEW GENERATION ANTHRACYCLINE THAT OVERCOMES MDR AND HAS NO CARDIAC TOXICITY FOR THE TREATMENT OF R/R AML

Background: Anthracyclines remain the backbone for induction therapy in the treatment of AML. Unfortunately, most patients will relapse with refractory disease and quickly succumb to their AML. One of the major reasons if not the major reason for developing resistance is the development of MDR. Annamycin was developed and has been shown both preclinically and clinically to overcome MDR and have no cardiac toxicity. Furthermore, it is formulated in a nanomolecular bi‐lamellar liposomal delivery mechanism that targets the leukemic cells in the bone marrow and spares cardiac and other normal cells. Therefore, a new phase I/II clinical trial has been started in both the US and Europe using L‐Annamycin for the treatment of all patients with R/R AML agnostic of mutational status. Aims: The aim of the phase I component is to determine the RP2D of L‐Annamycin for the treatment of R/R AML. The phase II component is designed to demonstrate efficacy leading to a phase II registration study for accelerated approval in both the US and EU. PK determinations are being performed for all patients. Methods: The phase I component is a standard modified Fibonacci 3+3 design to determine the RP2D. An additional 21 patients will be enrolled as an early determinant of efficacy at the RP2D. The sample size for this is based upon an expected response rate of 15%. Utilizing the optimized Simon two stage design, the assumption is that alpha = 0.1 and beta = 0.2. If less than 1 CR is observed in the first 14 subjects, the study will be stopped for futility. To be declared a success, at least 4 subjects of the 21 needs to demonstrate a CR. A DMC will monitor all data and decide if the study should continue and if any changes to the protocol are needed. Results: The study is ongoing in both Europe and the US. The first cohort has completed in the US. Even at the very low starting dose, one of the three patients had a near CR with just MRD after just one three‐day course of L‐Annamycin. The first cohort in Europe has enrolled two patients and updated results will be presented at the EHA Congress. Summary/Conclusion: Anthracyclines remain the backbone of induction therapy in AML but most patients will relapse and die from their refractory disease. Resistance develops because of MDR. L‐Annamycin overcomes this and has little to no cardiac toxicity even with up to eight cycles. This study will is designed to demonstrate its efficacy in all patients with R/R AML including the majority with no targetable mutations.