Dr Sweis on the Potential for XmAb819 to Fill Treatment Gaps in Refractory RCC

"We've had a tremendous advancement in the life expectancy, survival and progression-free survival with combination immunotherapy approaches over the last 10 years. However, when patients progress...there aren't great options."

Randy F. Sweis, MD, an assistant professor of medicine at the University of Chicago Medicine, discussed how the investigational drug XmAb819 is positioned to fill critical treatment gaps and address the massive unmet need present in refractory renal cell carcinoma (RCC), particularly for patients who have progressed after standard immunotherapy and VEGF TKI regimens.

He acknowledged that over the last decade, combination immunotherapy approaches have led to tremendous advancements in patient life expectancy, survival, and progression-free survival.

However, Sweis emphasized that substantial therapeutic challenges remain when patients progress after completing standard regimens. Specifically, limited good options exist for individuals who have already received VEGF TKI therapy or prior anti-PD-1 targeted therapy, regardless of whether that treatment included anti-CTLA-4 therapy.

Currently, the HIF2α inhibitor belzutifan (Welireg) is an available option for this patient population, and it is potentially moving into earlier use and future combination trials. Nonetheless, overall options beyond this agent remain limited.

Although cycling patients through various TKI therapies is an option, and some of maintain activity in the refractory setting, the primary unmet need is for drugs featuring truly novel mechanisms of action. Sweis noted that the T-cell engager approach utilized by XmAb819 is unique in RCC. Although this therapeutic strategy has been successful in treating other types of cancer, there are currently no approved drugs using this mechanism specifically for kidney cancer. Since patients are actively seeking alternatives after progressing on VEGF TKI and PD-1 therapies, Sweis concluded that XmAb819 addresses a significantly high unmet need in the refractory setting.