Dr. Jonasch on the Investigation of Belzutifan in ccRCC

Eric Jonasch, MD, professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of belzutifan (Welireg) in clear cell renal cell carcinoma (ccRCC).

The phase 1 LITESPARK-001 trial (NCT02974738) is evaluating belzutifan, a novel hypoxia-inducible factor-2α (HIF-2α) inhibitor, to determine the maximum tolerated dose and the recommended phase 2 dose in patients with advanced solid tumors.

Patients with previously treated, advanced ccRCC are among those enrolled in the trial, Jonasch says. Belzutifan blocks the interaction between the transcription factor HIF-2α with HIF-1β, preventing it to act as a transcription factor, Jonasch adds. The downstream consequence of this interaction is a decreased level of various pro-metabolic and proangiogenic genes, Jonasch explains.

Patients with ccRCC typically have an inactivation of the von Hippel-Lindau protein due to mutations or other modifications, Jonasch notes. This has prompted the exploration of belzutifan in this patient population, Jonasch concludes.