Eric Jonasch, MD, Discusses Use of MK-6482 in VHL Disease–Associated Kidney Cancer

May 30, 2020
Eric Jonasch, MD

The HIF-2a Inhibitor, MK-6482, induced clinical responses among patients with von Hippel-Lindau disease–associated renal cell carcinoma.

Treatment with MK-6482 appeared to be well tolerated and induced clinical responses among patients with von Hippel-Lindau disease (VHL)–associated renal cell carcinoma (RCC), according to study findings presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The trial showed an objective response rate (ORR) in RCC tumors per RECIST by independent review of 27.9%. Moreover, 8 patients who had an unconfirmed response showed an ORR of 41.0%. Additionally, 86.9% of patients had a decrease in the size of their target lesions and median time to response was 5.5 months.

Eric Jonasch, MD, professor of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, spoke to CancerNetwork about the results of the trial.



So, VHL disease at this time does not have an FDA approved therapy. It’s a hereditary disorder that affects the eyes, brain, spine, pancreas, adrenal glands, and kidneys. These individuals who have this – there are about 10,000, in the United States – basically face a lifetime of surveillance scans and surgical interventions or other types of interventions. 

So, having something that can actually shrink these without undergoing surgery would be a huge boost. 

This study, the primary aim was to assess shrinkage of renal carcinomas in these individuals with VHL disease to see whether or not we were able to shrink them with the drug (MK-6482).

This did result in shrinkage. Confirmed partial response in 28% of patients, and then a further 13% had unconfirmed responses. The only reason the 13% were not confirmed yet was because we didn’t have enough follow-up.

The rate of change and the rate of shrinkage was fairly consistent. So, when we do see shrinkage, we do see the continuation of shrinkage afterwards. So, that was primary and a very exciting read out of the study.

The key takeaway really is that we now have a therapy that seems to be effective, but also quite well tolerate. The side effect profile of this drug was quite reasonable. And there is also evidence, a number of areas affected by individuals with VHL disease. We also now have preliminary evidence that this is working in other manifestations – for example, hemangioblastomas, which affect the eye, the cerebellum in the spine – these seem to be shrinking with this drug. That is pretty unprecedented at this time in patients with VHL disease.