Abstract 4185: Randomized double-blind clinical study of F14512, a new polyamine-vectorized anticancer drug and Etoposide in naturally occurring canine lymphoma

F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in Phase I/II clinical trials in patients with acute myeloid leukemia. The aim of this study is to investigate the potential of F14512 in a new clinical indication and to compare its clinical efficacy with the reference topoisomerase II inhibitor Etoposide. Because of the many similarities between human and dog lymphomas, we are seeking to determine the tolerance, efficacy, PK/PD relationship of F14512 in this indication and potential biomarkers that could be translated into human trials. Firstly, we successfully initiated two Phase 1 dose-escalation trials with 23 and 27 dogs with naturally occurring lymphomas using F14512 and Etoposide, respectively, with endpoints including safety, therapeutic efficacy and biomarker studies. Secondly, we initiated a randomized double blind study with two groups of 24 dogs with naturally occurring lymphomas in order to compare the clinical efficacy of F14512 and Etoposide in both newly diagnosed and relapsing cases. The Phase 1 trial demonstrated that F14512 could be safely administered to dogs with lymphoma resulting in strong therapeutic efficacy with a response rate of 91% (21/23) with 10 complete responses, 11 partial responses, one stable disease and one progressive disease. Phosphorylation of histone H2AX was studied as a potential pharmacodynamic biomarker of F14512. Etoposide displayed modest therapeutic efficacy with a response rate of 19% (5/27) with 1 complete response, 4 partial responses, and 6 stable diseases. The comparative clinical study was then initiated with both compounds administered at the recommended dose identified in the Phase 1 trial. Inclusion of all the dogs from the randomized double blind comparative study will be finalized at the beginning of 2016 and the results of the study will be disclosed at the AACR 2016 meeting. This work shows that naturally occurring cancers in dogs can be of great interest in translational research in order to support preclinical and clinical development of new compounds. Citation Format: Bruno Gomes, Francois Serres, Juliette Hordeaux, Zacharie Segaoula, Emmanuel Bouchaert, Severine Wadoux, Laurent Marescaux, Franck Floch, Pierre Boye, Kevin Geeraert, Ingrid Bemelmans, Thierry Marchal, Corinne Fournel, Gregoire Zorza, Pierre Ferre, Aurelie Petain, Nicolas Guilbaud, Dominique Tierny. Randomized double-blind clinical study of F14512, a new polyamine-vectorized anticancer drug and Etoposide in naturally occurring canine lymphoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4185.