Abc-08: A Phase Ib, Multi-Centre, Open-Label Study Of A First-In-Class Nucleotide Analogue Nuc-1031 In Combination With Cisplatin In Patients With Locally Advanced/Metastatic Biliary Tract Cancers.

TPS544Background: The UK ABC-02 study established cisplatin and gemcitabine as the reference regimen for first-line treatment of patients (pts) with advanced biliary tract cancers (BTCs) (median overall survival (OS): 11.7 months). No clinical studies since ABC-02 have reported an extension in OS, and therefore effective new agents/combinations are required. NUC-1031 was designed to improve on gemcitabine’s relatively poor efficacy by overcoming its associated key cancer resistance mechanisms, through cellular uptake independent of nucleoside transporters, activation independent of deoxycytidine kinase and protection from cytidine deaminase inactivation, resulting in over 200x the intracellular levels of the anti-cancer metabolite, dFdCTP, greater stability and reduction in the generation of toxic metabolites. NUC-1031 showed activity as monotherapy in a phase I/II study in 7 pts with BTC, refractory to all standard treatments (Blagden et al ASCO 2015; abstract 2514). Methods: ABC-08 is a multi-centre pha...