Study Title: Casdatifan shows durable response linked to HIF-2α biology in kidney cancer
Publication: Nature July 1, 2026
Dana-Farber Cancer Institute authors: Toni K Choueiri, MD
Summary: The first-in-patient, single-arm ARC-20 clinical trial, led by Dana-Farber Cancer Institute's Toni K. Choueiri, MD, evaluated casdatifan, a next-generation HIF-2α inhibitor, as monotherapy for metastatic clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. Patients eligible for the study were previously treated with standard therapies. Most ccRCC tumors accumulate HIF-2α, which drives tumor growth and metastases. Casdatifan is a next-generation HIF-2α inhibitor designed for high potency and selectivity. A total of 127 patients enrolled and received a range of escalating doses. Results show that the treatment is well tolerated with manageable side effects that were consistent with expectations for HIF-2α inhibitors. Casdatifan also showed promising signs of efficacy, with objective responses in 35 percent of patients receiving a 100mg dose, the selected dose for future trials. Extensive blood and tissue biomarkers of HIF-2α inhibition and downstream pathway activation paralleled clinical benefit, suggesting that the therapy is hitting its target and working as expected mechanistically. Choueiri collaborates closely with William G. Kaelin Jr. at Dana-Farber, who shared the Nobel Prize in 2019 for discovering how cells sense and adapt to oxygen. An understanding of that biology ultimately led to HIF-2α targeting in kidney cancer.
Significance: Evidence from this trial supports continued study of casdatifan for ccRCC, including the PEAK-1 international randomized phase 3 trial comparing casdatifan plus cabozantanib to cabozantanib alone in patients with metastatic ccRCC whose cancer progressed after immunotherapy.
Funding: Arcus Biosciences, Inc.
