Casdatifan for the Treatment of Refractory Metastatic Clear Cell Renal Cell Carcinoma

PRIMARY OBJECTIVE: I. To determine the change in expression of predefined HIF2-regulated target genes in metastatic tumor tissue following casdatifan therapy in a refractory clear cell renal cell carcinoma (ccRCC) population. SECONDARY OBJECTIVES: I. To assess changes in global tumor gene expression following casdatifan treatment. II. To identify differences in baseline and on-treatment HIF-mediated gene expression between objective responders and non-responders. OUTLINE: Patients receive casdatifan orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI), tumor biopsy and blood sample collection throughout the study. Two dose reductions will be permitted in the event of drug-related adverse events, per protocol-defined criteria: * Reduced dose (-1): 50mg once daily * Reduced dose (-2): 25mg once daily Treatment will be discontinued if toxicity is not manageable at this reduced dose. After completion of study treatment, patients who discontinue treatment for reasons other than disease progression are followed up every 12 weeks thereafter. Casdatifan will be provided by Arcus. No additional therapeutic agents will be administered as part of this protocol.