Peloton Therapeutics, Inc. presented first-in-human Phase 1 clinical data on its lead investigational candidate, PT2385, at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago is the first clinical stage antagonist of hypoxia inducible factor-2a (HIF-2a), a transcription factor implicated in the development and progression of kidney and other cancers. Patients with advanced clear cell renal cell carcinoma and at least one prior therapy with a VEGF inhibitor were treated with PT2385 to determine the recommended Phase 2 dose and evaluate safety, pharmacokinetics and pharmacodynamics. Twenty-six patients were enrolled in dose escalation and received PT2385 from 100 to 1,800 mg twice per day. Patients were heavily pretreated prior to study entry, with greater than 50% having four or more prior therapies. Exposure increased with doses up to the 800 mg cohort without a further increase from 800 to 1,800 mg. No dose limiting toxicities were observed at any dose level. Circulating plasma levels of the HIF-2a transcriptional target erythropoietin rapidly decreased with treatment with PT2385 and remained suppressed. Based on safety, pharmacokinetic and EPO pharmacodynamic data, 800 mg twice per day was selected as the recommended Phase 2 dose. An additional 25 patients were enrolled in an expansion cohort at the recommended Phase 2 dose. Among the 51 patients in total, the most common all-grade adverse events (AEs) were anemia, peripheral edema and fatigue. No cardiovascular AEs were noted. To date, one patient had a complete response, three patients had a partial response, and 16 patients had stable disease for 16 or more weeks. 10% of patients remain in this ongoing clinical trial for at least one year.