Medicine Matters oncology

I had really the pleasure to present data from the first HIF2 inhibitor in clear-cell RCC at this wonderful meeting, GU 2020. So we enrolled 55 heavily pretreated patients with clear-cell RCC to go on MK-6482, which is first-in-class oral HIF2 inhibitor.

HIF2 is a transcription-- master transcription factor downstream of VHL an initial truncal event in clear-cell RCC-- was really undruggable, a transcription factor that was undruggable, until recently, some elegant crystallographic work showed that a small molecule like MK-6482 can go into one of those binding pockets and inhibit the downstream target.

Our initial experience with these 55 patients showed that the drug is well tolerated. 120 milligrams once a day was the dose to-- we proceeded for. Some of the side effects were anemia, hypoxia, but we did not see the cardiovascular toxicities seen normally with VEGF tyrosine kinase inhibitor. And, again, a refractory population, median number of prior line of therapy was three, with most of the patients receiving VEGF and PD-1, PD-L1 inhibitor.

Now, in terms of efficacy, the response rate after 13 months of follow-up was 24%, with 69% of patients having some degree of tumor shrinkage, and a progression-free survival rate of-- progression-free survival of 11 months. Interesting thing, when you look at the risk group, the favorable, the intermediate, and the poor, having set so most of the patients were in the intermediate, there were responses seen across risk groups, so across IMDC, favorable, good, and favorable, intermediate, and poor risk. So this is something exciting.

Now we're taking this to the next level with a phase 3 trial, a pivotal trial, post-VEGF, post-PD-1 inhibitor, that will enroll patients-- enroll over 700 patients with co-primary endpoint progression-free survival and overall survival, which plans also to combine MK-6482 with other targets, so some exciting news.