Abstract 2512: History and summary of current practices for assessment of drug-induced QT-prolongation in oncology drug development

Abstract The ICH E14 guideline issued in 2005 made the assessment of drug-induced QT-prolongation a mandatory step in the development of all new therapeutics. The guidance provided a clear requirement, however the means to achieve this requirement within the specific space of oncology clinical development remained challenging. Several updates to the guidelines, mainly in the form of Q&As published in 2012, 2015 and 2022 helped to clarify regulator expectations and thus determine the strategies available in a field where a straightforward investigation performed in Healthy Subjects (i.e. the dedicated TQT trial) is not feasible for reasons of drug tolerability ; a dedicated trial in the patient population also poses significant ethical questions in addition to logistical hurdles. Today, following the different updates to ICH E14 we feel that a clear strategy may be implemented by sponsors developing new treatments in the field of oncology. These strategies, which include in vitro and in vivo testing and a specific approach for ECG recordings in phase I, are followed by several companies, but are not yet universally included in development plans from their start. We thus believe that a simplified roadmap should hold value for professionals looking to develop novel oncology therapeutics. The focused and precise assessment of drug-induced QT prolongation also meets the needs of clinicians looking to assess this risk in complex clinical setting with multiple risk factors1, 2. The purpose of our abstract will be to provide a clear history of the evolution of the ICH E14 guideline and illustrate what could be the current practice implemented for new therapeutics in the field of oncology. Our main interest will be for NCEs who cannot be safely administered to Healthy Participants however approaches for NBEs will also be described, with illustrations of results. This will include a description of the in vivo preclinical and clinical strategies which can be followed. Citation Format: Louis-Guillaume Marquier, Frederique Lemaux-Duvillier, Stephanie Le Goaller, Philippe L'Hostis, Eric Delpy, Mathieu Grace, Jean-Louis Pinquier. History and summary of current practices for assessment of drug-induced QT-prolongation in oncology drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2512.