Dr. Choueiri on Phase I/II Data of MK-6482 in Advanced Clear Cell RCC

Toni K. Choueiri, MD, director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute, and Jerome and Nancy Kohlberg Chair and professor of medicine, Harvard Medical School, discusses phase I/II results of a trial evaluating the oral HIF-2 α inhibitor MK-6482 in patients with advanced clear cell renal cell carcinoma.

MK-6482 targets the transcription factor HIF-2, which is said to be very difficult to target and was thought to be undruggable, Choueiri explains. HIF-2 is an important target in clear cell RCC, he adds, because clear cell RCC is defined by VHL alteration that leads to upregulation in HIF-2. Earlier data have demonstrated that small molecules can enter one of the HIF-2 pockets and inhibit the heterodimerization; these data led to the development of molecules, such as MK-6482.

In this phase I/II study, investigators evaluated 55 previously treated patients with clear cell RCC; the median lines of prior therapy was 3. Results showed that the objective response rate with MK-6482 was 24%, with 69% of patients experiencing tumor shrinkage. Moreover, the median progression-free survival was 11 months, and responses were also observed in International Metastatic RCC Database Consortium poor-risk patients, Choueiri concludes.

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