A phase II study of M6620 and irinotecan in TP53 mutant gastric and gastroesophageal junction (GEJ) adenocarcinoma patients (pts) [NCT03641313].

TPS175Background: Progressive metastatic or unresectable gastric/GEJ adenocarcinoma pts carry dismal prognoses with a significant need for novel systemic therapies. One avenue for drug development in this disease is targeting salvage DNA repair pathways. TP53, a central gene to DNA damage repair (DDR), is mutated in 50% of gastric/GEJ cancer pts. Pre-clinical models from multiple cancer types demonstrate that cancer cells with TP53 mutations rely on the ataxia telangiectasia and Rad-3 related protein kinase (ATR) axis as a primary pathway of salvage DDR in the face of cytotoxic stress. The ATR pathway is typically triggered by single strand DNA breaks such as those generated by topoisomerase I inhibitors. Irinotecan is already known to be active in later line gastric/GEJ pts, thus, there appears to be an opportunity to combine the agent with the ATR inhibitor M6620 in TP53 mutant pts with the disease. Methods: Our trial is a single arm phase II study of M6620 plus irinotecan in progressive gastric/GEJ ade...