Project Summary This proposal is made in response to the NCI’s announcement for the Cancer Clinical Investigator Team Leadership Award. The aim of this funding opportunity is to support mid-level clinical investigators at NCI- designated Cancer Centers who actively enroll patients and participate in NCI-funded clinical trials in order to promote the retention of investigators in academic clinical research careers. This grant will be used to support my effort to expand accrual, awareness, and efficiency of early-phase clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Additionally, it will be used to continue and extend my work on two NCI-sponsored clinical trials and the related correlative research. The first trial is a proof-of- concept Phase II study evaluating EZH2 inhibition with tazemetostat in recurrent or persistent endometrioid or clear cell ovarian cancer, and endometrioid endometrial cancer (NRG-GY014). This national NRG Oncology protocol, for which I serve as Study Co-Chair, has an extensive biomarker analysis plan that will be led by me and performed at MSKCC. The second trial is a Phase I study of PIK3CB inhibition with AZD8186 in combination with docetaxel in PTEN or PIK3CB-mutated solid tumors. I am the Study Chair of this ETCTN trial and MSKCC serves as the central site for analysis of biomarkers, including tumor sequencing (integral biomarker), cell-free DNA sequencing, and immunohistochemistry. Both protocols exemplify my focus on precision medicine and utilize molecular features of cancer including tumor genomics to identify predictors of response and resistance to therapy on early-phase clinical trials. My overall goal is to improve research efficiency at MSKCC, become an independently funded clinical researcher in academia, maximize the clinical and biologic knowledge we gain from each trial I participate in, and ultimately improve patient care. This proposal supports the objectives of the Center’s P30 Cancer Center Support Grant.