decreased cell viability and induced DNA damage by an increase in pH2AX in ovarian cancer cells. ATRi with ATRIN119 had similar antiproliferative effects to PARPi in BRCA-mutant ovarian cancer cells. ATRIN119 had antitumor effects with minimal toxicity using a novel BRCA2-mutant patient-derived xenograft (PDX) model supporting a possible synthetic lethality mechanism. Conclusions: Strategies to optimize approaches capitalizing on synthetic lethality in HR-deficient ovarian cancers are needed. ATR inhibition with ATRIN119 is a viable therapeutic option and further preclinical work is ongoing to optimize bioavailability and to identify the maximum tolerated dose.