Dr Sweis on Next Steps for the Investigation of XmAb819 in RCC and Beyond

"We’re looking at different dosing routes, but once we select some dosing routes and doses that we believe will be beneficial to move forward with, then we will expand [our study of XmAb819] into a larger cohort in RCC. Ultimately, the goal is to bring this [therapy] to other tumors as well."

Randy F. Sweis, MD, an assistant professor of medicine at the University of Chicago Medicine, discussed next steps for the development of the XmAb 2+1 ENPP3/CD3-targeted bispecific antibody XmAb819 in renal cell carcinoma (RCC).

The agent is currently being evaluated in an ongoing phase 1 study (NCT05433142). This trial is enrolling patients with advanced RCC whose cancer has progressed despite receiving standard treatments.

The initial goal of this phase 1 trial is to identify safety signals associated with XmAb819, such as cytokine release syndrome, and develop strategies to mitigate these signals through various dosing approaches. Sweis explained that the ultimate goal of the trial is to determine the optimal dose of the agent. This involves a shift from the “old paradigm” of merely seeking the maximum tolerated dose (MTD). In addition to seeing whether an MTD of the agent exists, researchers are now focused on looking at minimally effective doses. The overall objective is to determine the optimal biologic dose that achieves necessary activity and simultaneously minimizes the risk of adverse effects. This focus on balancing efficacy and safety risk is a key component of the early-phase study, Sweis emphasized.

The trial is also assessing different administration routes, including both intravenous and subcutaneous dosing. Once researchers have selected a beneficial dosing strategy and route, the plan is to expand the study into a larger cohort specifically for patients with RCC.

Sweis highlighted that hopes for XmAb819 utility extend beyond the kidney cancer setting; the goal of this research paradigm is to evaluate the agent in tumor types defined by the expression of ENPP3. Future targets could include papillary kidney cancer, as well as non–small cell lung cancer and colon cancer, he concluded.