New Research Published in Nature Links Clinical Activity with HIF‑2a Biology in Advanced Kidney Cancer Patients Treated with Casdatifan

• This is the first study to comprehensively interconnect clinical outcomes from patients receiving a HIF-2a inhibitor with peripheral biomarker changes and associated tumor biology
• HIF-2a inhibition with casdatifan resulted in deep and sustained suppression of the hormone erythropoietin in blood (serum EPO), which correlated with higher response rates and longer progression-free survival (PFS)
• A pooled analysis from four monotherapy cohorts (n=121) of the ARC-20 study showed that advanced kidney cancer patients treated with casdatifan lived beyond a year without cancer progression (median PFS of 12.2 months) despite multiple prior treatments with other standard regimens

Excerpt from the Press Release:

HAYWARD, Calif.–(BUSINESS WIRE)–Arcus Biosciences, Inc. (NYSE: RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer and inflammatory and autoimmune diseases, today 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 (ccRCC). 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.

“This is the first study to comprehensively assess the relationship between HIF-2a inhibitor-associated suppression of serum EPO production with tumor biology and clinical outcomes,” said Toni K. Choueiri, M.D., director of the Lank Center for Genitourinary (GU) Oncology at Dana-Farber Cancer Institute, the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, and lead investigator of ARC-20. “These findings were elucidated in parallel with demonstrating the meaningful clinical benefit of casdatifan, an investigational, HIF-2a inhibitor in development for the treatment of kidney cancer. 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.”

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 (evaluated by RNA levels and tissue imaging), correlated with improved clinical outcomes during casdatifan treatment.

Click the button below to read the entire Press Release:

Continue Reading The Press Release