Novel Drug for Treatment of Advanced Clear Cell Renal Cell Carcinoma
A first-in-human study published in the Journal of Clinical Oncology revealed positive results with a novel compound for patients with previously treated advanced clear cell renal cell carcinoma (RCC). PT2385 is the first medication from a new class of drugs called hypoxia-inducible factor-2α (HIF-2α) antagonists.
"The combination of activity and tolerability is very encouraging," said corresponding author Kevin D. Courtney, MD, PhD, of The University of Texas Southwestern Medical Center in Dallas. "In our experience, this HIF-2α inhibitor offers a combination of safety and potential activity that is unique compared to current treatments for advanced kidney cancer."
In most cases of clear cell RCC, the von Hippel-Lindau tumor suppressor is inactivated, which allows the HIF-2α to be inappropriately stabilized. This leads to increased expression of some genes, including erythropoietin, which encourage tumor growth.
In this phase I, open-label, multicenter trial, 26 patients were included in the dose-escalation study. Eligible patients had locally advanced or metastatic clear cell RCC that had progressed during one or more prior regimens that included a vascular endothelial growth factor inhibitor. A complete response was observed in 2%; a partial response, in 12%; and stable disease, in 52% of participants. The most common all-grade adverse events were anemia (45%), peripheral edema (39%), and fatigue (37%).