Dr Toni Choueiri speaks to ecancer about activity and biomarker analyses with casdatifan (cas), a next-generation HIF-2α inhibitor, in refractory clear cell renal cell carcinoma (ccRCC).

He reviews updated results from the phase one ARC-20 study evaluating Cas, a novel hypoxia-inducible factor 2 alpha inhibitor, in patients with heavily pretreated metastatic clear cell renal cell carcinoma.

Cas demonstrated encouraging clinical activity, with response rates around 30 to 35 percent and prolonged progression-free survival.

Notably, the drug produced rapid and sustained reductions in serum erythropoietin, a key biomarker of hypoxia-inducible factor pathway activity. Greater reductions in this biomarker were associated with higher response rates and improved disease control, highlighting a potential link between target engagement and clinical benefit.

Treatment was generally well tolerated, with manageable side effects such as anaemia and low oxygen levels, and very low discontinuation rates.

These findings support Cas as a promising targeted therapy and reinforce the role of biomarker-driven approaches in advanced kidney cancer.