JPI-547 + modified FOLFIRINOX

JPI-547 + modified FOLFIRINOX is a combination therapy under investigation for solid tumors, particularly for those with homologous recombination repair (HRR) deficiencies, such as BRCA-mutated cancers and pancreatic ductal adenocarcinoma (PDAC). JPI-547 is a potent, orally available dual inhibitor of PARP1/2 (poly-ADP-ribose polymerase) and Tankyrase 1/2 (TNKS1/2), developed to target defects in DNA repair and modulate Wnt/β-catenin signaling. It shows enhanced antitumor activity compared to other PARP inhibitors, notably in both BRCA-deficient tumor models and in cancers with Wnt-addiction (such as those harboring mutations like RNF43 or APC). Modified FOLFIRINOX refers to an adjusted regimen of the standard FOLFIRINOX chemotherapy (oxaliplatin, irinotecan, leucovorin, and fluorouracil), which is typically dose-reduced or has altered administration schedules to improve tolerability. The combination is designed to exploit synthetic lethality in HR-deficient tumors and leverage additional cytotoxic mechanisms provided by chemotherapy.