Arcus Biosciences (RCUS) announced that a new study on the ARC-20 trial—which evaluated casdatifan in patients with metastatic clear cell renal cell carcinoma—has been published in Nature.
Published study evaluated the use of casdatifan, an investigational small-molecule HIF-2a inhibitor, as a monotherapy. According to the company’s statement, this study is the first to comprehensively demonstrate the relationship between HIF-2a inhibitor-induced changes in circulating serum EPO, tumor biology, and clinical activity.
This study reported that deeper suppression of serum EPO production in patients with clear cell renal cell carcinoma—a tumor driven by HIF-2a—was associated with clinical benefit. This included higher response rates and longer progression-free survival. The data demonstrated that casdatifan monotherapy achieved deep and sustained suppression of serum EPO and supported the use of EPO as a biomarker for HIF-2a inhibition.
In addition, the study found that high HIF-2a pathway activity was associated with better clinical outcomes during casdatifan treatment. This activity was assessed through the expression of key genes in the HIF-2a pathway and baseline tumor EPO levels. Arcus stated that these findings establish a strong link between HIF-2a-focused tumor biology and outcomes in patients receiving casdatifan treatment.
In the study, which focused on various cohorts of the ARC-20 platform trial, casdatifan monotherapy was evaluated at doses of 50 mg twice daily, 50 mg once daily, 100 mg once daily, and 150 mg once daily. The majority of patients had previously experienced disease progression after at least two prior treatment lines, which included anti-PD-1 and VEGFR TKI therapies. In the pooled analysis, more than half of the patients had received at least three prior treatment lines, and more than a quarter had received at least four.
As of the data cut-off date, casdatifan was reported to demonstrate durable antitumor activity. In the 100 mg once-daily tablet cohort, the confirmed objective response rate was reported as 35%, while the median progression-free survival had not yet been reached. Approximately 60% of patients in this cohort remained progression-free at month 12.
In a pooled analysis of the four monotherapy cohorts, the confirmed objective response rate was 31%, and the median progression-free survival was 12.2 months. It was also noted that tumor shrinkage continued beyond 12 months of treatment.
In a subsequent analysis conducted after the results were submitted for publication—with a data cut-off date of January 30, 2026—the median progression-free survival in the 100 mg once-daily cohort, which uses the same dose and formulation as the ongoing PEAK-1 Phase 3 trial, was reported as 15.1 months.
No unexpected signals were detected during the Casdatifan safety studies
On the safety front, it was noted that no unexpected safety signals were observed as of the August 2025 data cut-off date, and that casdatifan had an acceptable and manageable safety profile across all doses. Anemia and hypoxia were reported as the most common class-related adverse events. No patients in any of the four cohorts discontinued treatment due to anemia, while three patients discontinued treatment due to hypoxia.
Arcus Biosciences outlined its casdatifan development strategy as a TKI-free first-line casdatifan-based treatment for physicians and patients, a first-line combination regimen containing a TKI, a HIF-2a inhibitor treatment built upon cabozantinib—the standard second-line therapy—and late-stage treatment options that have been confirmed to provide clinical benefit even in patients who have previously received HIF-2a inhibitor-based therapy.
