Discussion
ovarian cancer, tumors, heterogeneous tumors, treatment-resistant
OVARIAN CANCER, TUMORS
Here we present results from the phase 1 TRESR study, which represents, to our knowledge, the most comprehensively analyzed, prospectively selected cohort of tumors treated with ATRi monotherapy to date. The safety and tolerability profile of camonsertib was consistent with a highly selective and potent ATRi, and preliminary anti-tumor activity was demonstrated in heavily pre-treated tumors across a range of histologic types and enrollment gene alterations.Since the discovery of synthetic lethality and the approval of PARPis in multiple Within the ovarian cancer subset, camonsertib anti-tumor activity was observed in patients with Time to response was shorter in patients with Notably, TRESR also included patients harboring DDR-altered genes for which no targeted standard-of-care therapy exists, such as These observations suggest that a better understanding of the factors that predict clinical responses to ATRi is needed to help guide the design of future trials developing ATRisInterestingly, responses were observed in two patients with monoallelic To better understand the optimal method for identifying The relatively high prevalence of We also evaluated whether ctDNA changes can serve as a surrogate marker of therapeutic response, as previously reportedThis study has several limitations. As an early-phase trial, TRESR is a non-comparative study in a heavily pre-treated patient population with genomically complex, treatment-resistant, heterogeneous tumors. Enrolling patients with tumors harboring pathogenic mutation genes other than The results of the TRESR trial highlight the utility of pre-clinical results from chemogenomic CRISPR–Cas9 screens and small-scale validation experiments