Arcus Biosciences Publishes ARC-20 Study Results
Arcus Biosciences announced a publication in Nature describing new research from the ARC-20 study. The publication evaluated casdatifan, an investigational, small-molecule HIF-2a inhibitor, as a monotherapy in patients with metastatic clear cell renal cell carcinoma. It is the first study to comprehensively describe the relationship between HIF-2a inhibitor-associated changes in circulating serum EPO, tumor biology and corresponding clinical activity. The study showed that in ccRCC patients with HIF-2a-driven tumors, deeper suppression of HIF-2a-associated production of serum EPO correlated with clinical benefit, including higher response rates and longer PFS. The data showed that casdatifan monotherapy resulted in deep and sustained suppression of serum EPO, further validating EPO as a biomarker of HIF-2a inhibition. Deep suppression of serum EPO was correlated with higher response rates and longer PFS. High HIF-2a activity, as determined by expression of key genes in the HIF-2a pathway and baseline tumor EPO levels, correlated with improved clinical outcomes during casdatifan treatment. Taken together, these measures consistently supported the same conclusion and provide strong evidence linking the biology of HIF-2a-driven tumors to patient outcomes with casdatifan. Arcus's holistic development strategy is intended to provide physicians and patients with: a casdatifan-based TKI-sparing first-line treatment; a casdatifan-based TKI-inclusive first-line regimen; a second-line HIF-2a inhibitor treatment that builds on the second-line standard-of-care TKI, cabozantinib; and a late-line therapy that has been clinically validated to also provide benefit in patients previously treated with a HIF-2a inhibitor-based therapy. This research focused on various cohorts of the ARC-20 platform study that evaluated casdatifan monotherapy in patients with metastatic ccRCC. Four monotherapy cohorts were included, across doses of 50mg twice daily, 50mg once daily, 100mg QD and 150mg QD. Most of the patients had progressed on at least two prior lines of therapy, including both an anti-PD-1 and a VEGFR TKI. The patient population was heavily pretreated; in the pooled analysis, more than half of patients received at least three prior lines of therapy, and more than one quarter had received at least four prior lines of therapy. Most patients had an International Metastatic Renal Cell Carcinoma Database Consortium risk factor of intermediate or poor. At the time of the data cutoff, casdatifan produced durable antitumor activity. In the 100mg QD tablet cohort, the confirmed objective response rate was 35% and median PFS had not yet been reached, with 60% of patients remaining progression-free at 12 months. In the pooled analysis of all four monotherapy cohorts, cORR was 31% and mPFS was 12.2 months, with continued reductions in tumor size observed beyond 12 months of treatment. In a later analysis with a January 30, 2026 DCO, conducted after these results were submitted for publication, mPFS was 15.1 months in the 100mg QD cohort, the same dose and formulation being used in the ongoing PEAK-1 Phase 3 study. At the time of the August 2025 DCO, no unexpected safety signals were observed, and casdatifan had an acceptable and manageable safety profile across all doses. The most common class-effect events were anemia and hypoxia; across all four cohorts, no patients discontinued treatment due to anemia, and three patients discontinued due to hypoxia.
