SETD2 and cancer: Although therapeutic development of adavosertib has been in combination with other therapies (DNA damage repair targets such as PARP inhibitors and cytotoxic chemotherapy), we sought to evaluate single-agent activity in SETD2-altered solid tumor malignancies with a particular emphasis on ccRCC, given the significant and durable tumor regressions observed in preclinical studies, with the potential to have less adverse events and improved toxicity profiles compared with its use in combination with other cancer-directed therapies.