Ramaprasad Srinivasan, MD, PhD, on Next Steps for MK-6482 in VHL-Associated Disease

Study results indicated that the small molecule HIF-2α inhibitor MK-6482 induced positive results in patients with certain Von Hippel-Lindau disease–associated solid tumors.

A study presented at the Society of Urologic Oncology (SUO) 21st Annual Meeting indicated that MK-6482 demonstrated durable efficacy in patients with Von Hippel-Lindau (VHL) disease–associated clear cell renal cell carcinoma (ccRCC), pancreatic lesions, and hemangioblastomas by targeting the underlying pathophysiology of the disease.

In addition, investigators also found that the safety profile of the oral HIF-2α inhibitor was favorable in the study population.

In an interview with CancerNetwork®, Ramaprasad Srinivasan, MD, PhD, investigator and head of the Molecular Cancer Therapeutics Section in the Center for Cancer Research at the National Cancer Institute, discussed the next steps for this study and what he believes the future holds for patients with VHL-associated disease.

As you may or may not know, the FDA, based on preliminary results that we have from the study, has granted breakthrough [therapy] designation for [MK-6482]. To me, [this] indicates that there is sufficient promise with this drug [and] that the FDA is willing to consider potential indication for this drug in patients with VHL [disease]. That’s an ongoing process, and the FDA will eventually decide whether or not the data warrant approval of this drug.

A lot of the future plans for this agent and this disease are going to depend on FDA input. There are several areas I can think of where this drug could eventually be either utilized or further evaluated. We, of course, will continue to follow, at this point, patients who are already on this study, with a [goal of] getting more information on long-term efficacy [and] long-term durability because these are important concepts. VHL is a chronic disease and we would like whatever intervention we [use] to have long term impacts, and so I think long term follow up is going to be key.

It’s also going to be very important for us to see whether we’re actually making a difference in the clinical course, or the natural history, of interventions that we normally offer patients with VHL. For instance, yes, we are shrinking these tumors, but are those enough and sustained enough for us to go away from surgery in these patients? In other words, are we able, with this drug, to minimize the need for surgery in these patients. I think those are important things that we’d like to look at and continue to follow.

We also, at this point, assume that shrinking these tumors means that what we do with surgery can be recapitulated by what we do with this drug. In particular, we think that by shrinking these tumors or by keeping them below 3 cm, we minimize the risk of metastatic spread just as we would with surgical excision of tumors that reach 3 cm or more in size. But that’s another issue I think that we need to follow up [on] long term and ensure that the hypothesis is indeed correct. Again, we can think of a variety of other situations in which we can evaluate this drug, but I think time will tell how [these findings]…best apply and are best further evaluated.