Timothy Yap, MBBS, PhD, MRCP, PgDip, University of Texas MD Anderson Cancer Center, Houston, TX, outlines updates from the Phase I/II TRESR trail (NCT04497116) which assessed RP-3500, a ataxia telangiectasia and Rad3-related inhibitor (ATRi), in patients with DNA damage repair (DDR) loss-of-function mutant tumors. RP-3500 was well tolerated, with no grade 4 mechanism-based anemia events seen in the trial and grade 3 events occurring at a rate of 24%. Moreover, RP-3500 monotherapy resulted in durable clinical benefits in several tumor types and genomic alterations, with the overall clinical benefit rate being 43%. Importantly, in patients with ovarian cancer, 85% of whom were platinum-refractory and resistant, and 90% of whom had previously been treated with a PARP inhibitor, the overall response rate was 25%, the clinical benefit rate was 75%, and the median progression-free survival was 35 weeks. In patients with BRCA1 and BRCA2 mutated cancers who were previously treated with a PARP inhibitor, the clinical benefit was 48%. Many clinical trials investigating RP-3500 alone and in combination with other agents are currently being undertaken. This interview took place at the American Association for Cancer Research Annual Meeting in New Orleans, LA.