Abstract A015: Rationale for the use of pulsed rather than continual dosing of the novel Focal Adhesion Kinase inhibitor AMP945 in pancreatic cancer

Abstract

Abstract Amplia Therapeutics Limited is developing AMP945, a highly selective inhibitor of Focal adhesion kinase (FAK) for the treatment of pancreatic cancer in combination with standard of care gemcitabine and nab-paclitaxel.1 FAK has been associated with the activity of myofibroblasts and collagen deposition and remodeling in PDAC. In preclinical studies, AMP945 displays potent anti-fibrotic activity in vitro and in vivo. In mouse models of PDAC, pulsed dosing of AMP945 added to gemcitabine and nab-paclitaxel inhibited collagen deposition and cross-linking and potentiated the effect of chemotherapy leading to increased survival.2A Phase 1 trial of AMP945 has been completed in which AMP945 showed excellent safety, tolerability, and pharmacokinetic properties as well as pharmacodynamic evidence of target engagement. Amplia’s recently initiated Phase 1b/2a clinical trial AMP945-PC-2013 (ACCENT) will assess a pulse dosing regimen of AMP945 in combination with gemcitabine and nab-paclitaxel as first-line therapy in patients with advanced pancreatic cancer. In ACCENT, patients will undergo a one-week oral loading dose of AMP945 and will be pulse dosed for four days prior to IV administration of gemcitabine and nab-paclitaxel, given according to a standard treatment schedule. Once daily oral dosing has anticipated benefits in terms of limitation of risk of acquired resistance, minimal potential for drug-drug interactions, adherence to therapy, and allows patients to self-administer AMP945 with the aim of potentiating response to standard of care chemotherapy. This abstract presentation will report on AMP945’s development status and the clinical rationale and status of the ACCENT trial. 1. Von Hoff et al., N Engl J Med 2013; 369:1691-1703 2. Murphy KJ et al. Sci Adv. 2021 Oct;7(40):eabh0363. 3. https://clinicaltrials.gov/ct2/show/NCT05355298 Citation Format: John Lambert, Mark Devine, Anthony Bishop. Rationale for the use of pulsed rather than continual dosing of the novel Focal Adhesion Kinase inhibitor AMP945 in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A015.