Arcus Biosciences (NYSE: RCUS) announced the publication of research in Nature from its ARC-20 study evaluating casdatifan, an investigational HIF-2a inhibitor, as a monotherapy in patients with metastatic clear cell renal cell carcinoma (ccRCC).

The study, according to the company, is the first to examine the relationship between HIF-2a inhibitor-associated changes in circulating serum erythropoietin (EPO), tumor biology, and clinical outcomes. Researchers found that deeper suppression of serum EPO correlated with higher response rates and longer progression-free survival (PFS).

In a pooled analysis of four monotherapy cohorts (n=121), the confirmed objective response rate was 31% and median PFS was 12.2 months. More than half of patients (55%) had received at least three prior lines of therapy. In the 100mg once-daily tablet cohort — the dose being used in the ongoing Phase 3 PEAK-1 study — the confirmed response rate was 35%, with 60% of patients remaining progression-free at 12 months as of the August 2025 data cutoff.

A later analysis with a January 2026 cutoff showed median PFS of 15.1 months in the 100mg once-daily cohort.

Serious treatment-emergent adverse events occurred in 31% of patients across both the Phase 3 dose cohort and the pooled analysis. The most common class-effect events were anemia and hypoxia. No patients discontinued treatment due to anemia; 2% discontinued due to hypoxia across all four cohorts.

"Patients treated with casdatifan had a median progression-free survival of over one year despite half of patients having progressed on three or more prior treatments with other standard therapies," said Toni K. Choueiri, M.D., of Dana-Farber Cancer Institute and lead investigator of ARC-20.

Arcus said it expects to complete enrollment in the PEAK-1 Phase 3 study and initiate a Phase 3 study in the first-line metastatic ccRCC setting by year-end 2026. Casdatifan has not received regulatory approval, and its safety and efficacy have not been established.